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1'-Acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression

Sok SPM, Ori D, Wada A, Okude H, Kawasaki T, Momota M, et al.

Int Immunol, 2021 06 18;33(7):373-386.
PMID: 33830232 DOI: 10.1093/intimm/dxab016

The nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing (NLRP) 3 inflammasome is a multiprotein complex that triggers Caspase-1-mediated IL-1β production and pyroptosis, and its dysregulation is associated with the pathogenesis of inflammatory diseases. 1'-Acetoxychavicol acetate (ACA) is a natural compound in the rhizome of tropical ginger Alpinia species with anti-microbial, anti-allergic and anti-cancer properties. In this study, we found that ACA suppressed NLRP3 inflammasome activation in mouse bone marrow-derived macrophages and human THP-1 monocytes. ACA inhibited Caspase-1 activation and IL-1β production by NLRP3 agonists such as nigericin, monosodium urate (MSU) crystals, and ATP. Moreover, it suppressed oligomerization of the adapter molecule, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1-mediated cleavage of pyroptosis executor Gasdermin D. Mechanistically, ACA inhibited generation of mitochondrial reactive oxygen species (ROS) and prevented release of oxidized mitochondrial DNA, which trigger NLRP3 inflammasome activation. ACA also prevented NLRP3 inflammasome activation in vivo, as evidenced in the MSU crystal-induced peritonitis and dextran sodium sulfate-induced colitis mouse models accompanied by decreased Caspase-1 activation. Thus, ACA is a potent inhibitor of the NLRP3 inflammasome for prevention of NLRP3-associated inflammatory diseases.

Matched MeSH terms: Phagocytosis/drug effects
3,5-Bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one, a Novel Curcumin Analogue, Inhibits Cellular and Humoral Immune Responses in Male Balb/c Mice

Arshad L, Jantan I, Bukhari SNA, Fauzi MB

Curr Pharm Biotechnol, 2018;19(6):468-482.
PMID: 29968535 DOI: 10.2174/1389201019666180703092723

BACKGROUND: 3,5-Bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one (BBP), a novel synthetic curcumin analogue has previously been shown to manifest potent immunosuppressive effects on the in vitro phagocytosis process of human neutrophils.
OBJECTIVE: In the present study, BBP was investigated for it's in vivo innate and adaptive immune responses mediated by different humoral and cellular immune factors.
METHODS: Male Balb/c mice were orally fed with BBP (5, 10 and 20 mg/kg) for a period of 14 days and immunized with sheep red blood cells (sRBC) on day 0 for the determination of adaptive responses. The effects of BBP on phagocytosis process of neutrophils isolated from blood of treated/untreated animals were determined. The ceruloplasmin and lysozyme serum levels and myeloperoxidase (MPO) plasma level were also monitored. The mechanism was further explored by assessing its effects on the proliferation of T and B lymphocytes, T-lymphocytes subsets CD4+ and CD8+ and on the secretion of Th1/Th2 cytokines as well as serum immunoglobulins (IgG, IgM) and delayed type hypersensitivity (DTH) reaction.
RESULTS: BBP showed a significant dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity and reactive oxygen species (ROS) production. In comparison to the sensitized control group, a dose-dependent inhibition was observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines. Moreover, a statistically significant decrease was perceived in serum levels of ceruloplasmin, lysozyme and immunoglobulins and MPO plasma level of BBP-treated mice. BBP also dose-dependently inhibited sheep red blood cells (sRBC)-induced swelling rate of mice paw in DTH.
CONCLUSION: These findings suggest the potential of BBP as a potent immunosuppressive agent.

Matched MeSH terms: Phagocytosis/drug effects
Fulltext 4,5,4'-Trihydroxychalcone, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol and rutin from Gynura segetum inhibit phagocytosis, lymphocyte proliferation, cytokine release and nitric oxide production from phagocytic cells

Yuandani, Jantan I, Husain K

BMC Complement Altern Med, 2017 Apr 11;17(1):211.
PMID: 28399868 DOI: 10.1186/s12906-017-1726-z

BACKGROUND: Gynura segetum is used traditionally to treat various ailments related to the immune system, which include cancer, inflammation, rheumatism, diabetes, hypertension, and viral infections but little studies have been carried out to validate their ethnopharmacological aspects. In this study the immunosuppressive effects of G. segetum and its constituents were investigated.
METHODS: Isolation of compounds from G. segetum leaves was conducted using vacuum liquid chromatography (VLC) and column chromatography (CC). Two new compounds, namely 4,5,4'-trihydroxychalcone and 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol, together with stigmasterol and β-sitosterol were isolated from G. segetum methanol extract and their structures were determined spectroscopically. The presence of gallic acid and rutin in the extract was determined quantitatively by a validated HPLC method. G. segetum methanol extract and its constituents were investigated for their effects on chemotaxis, phagocytosis, β2 integrin (CD18) expression, and reactive oxygen species (ROS) of polymorphonuclear leukocytes (PMNs), lymphocytes proliferation, cytokine release and nitric oxide (NO) production of phagocytes.
RESULTS: All the samples significantly inhibited all the innate immune responses tested except CD 18 expression on surface of leukocytes. Among the samples, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol exhibited the strongest inhibitory on chemotaxis, phagocytosis, ROS and NO production. The compound exhibited exceptionally strong inhibitions on ROS and chemotaxis activities with IC50 values lower than the positive controls, aspirin and ibuprofen, respectively. 4,5,4'-Trihydroxychalcone revealed the strongest immunosuppressive activity on proliferation of lymphocytes (IC50 value of 1.52 μM) and on release of IL-1β (IC50 value of 6.69 μM). Meanwhile rutin was the most potent sample against release of TNF-α from monocytes (IC50, 16.96 μM).
CONCLUSION: The extract showed strong immunosuppressive effects on various components of the immune system and these activities were possibly contributed mainly by 4,5,4'-trihydroxychalcone, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol and rutin.

Matched MeSH terms: Phagocytosis/drug effects
An electronmicroscopic study of the interaction of Burkholderia pseudomallei and human macrophages

Nathan SA, Puthucheary SD

Malays J Pathol, 2005 Jun;27(1):3-7.
PMID: 16676686

B. pseudomallei has been shown to persist intracellularly in melioidosis patients until reactivated by decreasing immunocompetence. We have shown by transmission electron microscopy the internalization of B. pseudomallei by human macrophages via conventional phagocytosis enclosed within membrane-bound vacuoles or phagosomes. Ferritin labeled lysosomes provided evidence of phagosome-lysosome fusion. Ingested bacilli were designated as "intact" or "damaged" on the basis of their ultrastructural features. An intact bacterium was seen with low electron opaque central nuclear region surrounded by dense bacterial cytoplasm, bounded externally by bacterial plasma membrane and cell wall. In contrast, B. pseudomallei were considered damaged when seen with cavitation within the central nuclear region, separation of bacterial cytoplasm from the cell wall, herniation of cytoplasmic contents and lamination of bacterial cell wall and its surrounding electron transparent zone. Our observations indicate that the microbicidal mechanism(s) in B. pseudomallei-infected macrophages failed to ensure complete clearance of the organism and this failure probably facilitates intracellular persistence and proliferation, and this may be one of the survival strategies adopted by this organism.

Matched MeSH terms: Phagocytosis*
Fulltext Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface

Quintana MDP, Ch'ng JH, Moll K, Zandian A, Nilsson P, Idris ZM, et al.

Sci Rep, 2018 02 19;8(1):3262.
PMID: 29459776 DOI: 10.1038/s41598-018-21026-4

Naturally acquired antibodies to proteins expressed on the Plasmodium falciparum parasitized red blood cell (pRBC) surface steer the course of a malaria infection by reducing sequestration and stimulating phagocytosis of pRBC. Here we have studied a selection of proteins representing three different parasite gene families employing a well-characterized parasite with a severe malaria phenotype (FCR3S1.2). The presence of naturally acquired antibodies, impact on rosetting rate, surface reactivity and opsonization for phagocytosis in relation to different blood groups of the ABO system were assessed in a set of sera from children with mild or complicated malaria from an endemic area. We show that the naturally acquired immune responses, developed during malaria natural infection, have limited access to the pRBCs inside a blood group A rosette. The data also indicate that SURFIN4.2 may have a function at the pRBC surface, particularly during rosette formation, this role however needs to be further validated. Our results also indicate epitopes differentially recognized by rosette-disrupting antibodies on a peptide array. Antibodies towards parasite-derived proteins such as PfEMP1, RIFIN and SURFIN in combination with host factors, essentially the ABO blood group of a malaria patient, are suggested to determine the outcome of a malaria infection.

Matched MeSH terms: Phagocytosis
Fulltext Antibody-dependent cellular phagocytosis of tropomyosin receptor kinase C (TrkC) expressing cancer cells for targeted immunotherapy

Lai PS, Usama SM, Kiew LV, Lee HB, Chung LY, Burgess K, et al.

Cancer Immunol Immunother, 2022 Sep;71(9):2099-2108.
PMID: 35032175 DOI: 10.1007/s00262-022-03147-y

Conventional cancer therapies such as chemotherapy are non-selective and induce immune system anergy, which lead to serious side effects and tumor relapse. It is a challenge to prime the body's immune system in the cancer-bearing subject to produce cancer antigen-targeting antibodies, as most tumor-associated antigens are expressed abundantly in cancer cells and some of normal cells. This study illustrates how hapten-based pre-immunization (for anti-hapten antibodies production) combined with cancer receptor labeling with hapten antigen constructs can elicit antibody-dependent cellular phagocytosis (ADCP). Thus, the hapten antigen 2,4-dinitrophenol (DNP) was covalently combined with a cancer receptor-binding dipeptide (IYIY) to form a dipeptide-hapten construct (IYIY-DNP, MW = 1322.33) that targets the tropomyosin receptor kinase C (TrkC)-expressed on the surface of metastatic cancer cells. IYIY-DNP facilitated selective association of RAW264.7 macrophages to the TrkC expressing 4T1 cancer cells in vitro, forming cell aggregates in the presence of anti-DNP antibodies, suggesting initiation of anti-DNP antibody-dependent cancer cell recognition of macrophages by the IYIY-DNP. In in vivo, IYIY-DNP at 10 mg/kg suppressed growth of 4T1 tumors in DNP-immunized BALB/c mice by 45% (p

Matched MeSH terms: Phagocytosis
Fulltext Cell surface proteins of cryptococcus neoformans mediate adherence and internalisation into mammalian cells

Choo, K.K., Chin, V.K., Chong, P.P., Ho, S.H., Yong, V.C.

JUMMEC, 2019;22(2):24-30.
MyJurnal

Cryptococcus neoformans is an encapsulated fungal pathogen that causes severe disease primarily in
immunocompromised patients. Adherence and internalisation of microbial pathogens into host cells often
begin with engagement of microbes to the surface receptors of host. However, the mechanisms involved
remain poorly understood. In this study, we investigated the association of cell surface determinants of C.
neoformans with mammalian cells. Our results showed that treatment with trypsin, but not paraformaldehyde
or heat killing, could reduce host-cryptococci interaction, suggesting the involvement of cell surface proteins
(CSPs) of C. neoformans in the interaction. We extended our investigations to determine the roles of CSPs
during cryptococci-host cells interaction by extracting and conjugating CSPs of C. neoformans to latex beads.
Conjugation of CSPs with both encapsulated and acapsular C. neoformans increased the association of latex
beads with mammalian alveolar epithelial cells, alveolar macrophages and monocyte-derived macrophages.
Further examination on the actin organisation of the host cells implied the involvement of actin-dependent
phagocytosis in the internalisation of C. neoformans in CSP-conjugated latex beads. We hypothesised that
CSPs present on the cell wall of C. neoformans mediate the adherence and actin-dependent phagocytosis
of cryptococci by mammalian cells. Our results warrant further studies on the exact role of CSPs in the
pathogenesis of cryptococcosis.

Matched MeSH terms: Phagocytosis
Changes in cellular immunity during chemotherapy for primary breast cancer with anthracycline regimens

Wijayahadi N, Haron MR, Stanslas J, Yusuf Z

J Chemother, 2007 Dec;19(6):716-23.
PMID: 18230556

Anthracyclines are the most widely used anticancer agents for breast cancer, of which doxorubicin and epirubicin have been reported to have equal efficacy. Unfortunately, the integrity of the immune system of breast cancer patients is severely affected by chemotherapy. This study compared the effect of combination chemotherapy with epirubicin (5-fluorouracil, epirubicin, cyclophosphamide (FEC)) and doxorubicin (5-fluorouracil, doxorubicin, cyclophosphamide (FDC)) regimens on subsets of the immune cells of patients with primary malignant breast tumors. Our aim was to determine the best regimen that produces the least degree of myelosuppression. Blood from 80 breast cancer patients undergoing chemotherapy (40 FEC and 40 FDC) was taken before chemotherapy and after every cycle (3 weeks) for 6 cycles. Blood was also taken from 40 normal healthy donors who served as normal control. Subsets of lymphocytes T-helper cells (CD3(+)CD4(+)), T-cytotoxic cells (CD3(+) CD8(+)), B-cells (CD19(+) CD20(+)) and NK cells (CD16(+)/CD56(+)CD3(-)) were analyzed by flow cytometry (FacsCalibur, BD) using monoclonal antibodies (Multitest, BD). All patients in the FEC and FDC groups suffered from myelosuppressive side effects. Both regimens led to an increase in the counts of monocytes but decreased polymorphonuclear cells (PMNs) and lymphocytes. Percentages of T-cytotoxic cells and NK cells were increased, but the percentage of B-cells was dramatically decreased. The phagocytic and intracellular killing ability of PMNs were also suppressed (p<0.01). No significant difference was found between the epirubicin-based regimen and doxorubicin-based regimen with regard to numbers of immune cells, percentages of lymphocytes subsets, Th/CTL ratio, engulfment and killing abilities of PMNs. In conclusion, we found that the epirubicin-based regimen is not superior to the doxorubicin-based regimen with respect to their toxicity of the immune cells, Th/CTL ratio and PMN count and functions. Moreover, both FEC and FDC regimens appear to conserve the cell-mediated immunity response needed for fighting against cancer cells.

Matched MeSH terms: Phagocytosis
Chediak-Higashi syndrome: a case report

Jayaranee S, Menaka N

Malays J Pathol, 2004 Jun;26(1):53-7.
PMID: 16190108

A 5-month-old Chinese male infant was referred to the University Hospital, Kuala Lumpur for persistent fever, generalised rash and abdominal distension. Clinically he was suspected to have haemophagocytic lymphohistiocytosis. Haematological findings including the presence of several abnormal giant granules in neutrophils and single large azurophilic granules in many lymphocytes and monocytes in the peripheral blood established the diagnosis of Chediak-Higashi syndrome. The patient responded to allogeneic bone marrow transplant. This paper discusses the characteristic features, clinical course and management of this rare disorder. We suggest that peripheral blood film examination for the abnormal giant granules in granulocytes is an essential investigation in all young children with frequent recurrent infections or who are suspected to have virus-associated haemophagocytic syndrome or familial haemophagocytic lymphohistiocytosis.

Matched MeSH terms: Phagocytosis
Fulltext Chlamydia and Its Many Ways of Escaping the Host Immune System

Wong WF, Chambers JP, Gupta R, Arulanandam BP

J Pathog, 2019;2019:8604958.
PMID: 31467721 DOI: 10.1155/2019/8604958

The increasing number of new cases of Chlamydia infection worldwide may be attributed to the pathogen's ability to evade various host immune responses. Summarized here are means of evasion utilized by Chlamydia enabling survival in a hostile host environment. The pathogen's persistence involves a myriad of molecular interactions manifested in a variety of ways, e.g., formation of membranous intracytoplasmic inclusions and cytokine-induced amino acid synthesis, paralysis of phagocytic neutrophils, evasion of phagocytosis, inhibition of host cell apoptosis, suppression of antigen presentation, and induced expression of a check point inhibitor of programmed host cell death. Future studies could focus on the targeting of these molecules associated with immune evasion, thus limiting the spread and tissue damage caused by this pathogen.

Matched MeSH terms: Phagocytosis
Fulltext Chronic granulomatous disease--a report in two Malay families

Mohd Noh L, Noah RM, Wu LL, Nasuruddin BA, Junaidah E, Ooi CP, et al.

Singapore Med J, 1994 Oct;35(5):505-8.
PMID: 7701372

Chronic granulomatous disease (CGD) is a very rare disease whose defect lies in an abnormal intracellular killing resulting in recurrent abscesses, lymphadenitis and granuloma formation. We describe 2 Malay male infants with CGD whom we believe to be the first report of this disorder in Malays. Both children presented with recurrent abscesses, pneumoniae and hepatosplenomegaly; lymphadenopathy was also present in one of the patients. The organisms isolated were catalase positive bacteria. Both neutrophil chemiluminescence (against fungal and bacterial antigens, phorbol myristate acetate) and intracellular killing assays were severely depressed. Recognition of CGD is important as great strides have been made in the treatment of this disease which include gamma interferon therapy besides the conventional prophylactic antibacterial therapy.

Matched MeSH terms: Phagocytosis
Fulltext Dendritic cells pulsed with generated tumor cell lysate from Phyllanthus amarus Schum. & Thonn. induces anti-tumor immune response

Mohamed SIA, Jantan I, Nafiah MA, Seyed MA, Chan KM

BMC Complement Altern Med, 2018 Aug 06;18(1):232.
PMID: 30081891 DOI: 10.1186/s12906-018-2296-4

BACKGROUND: Dendritic cells (DCs) are unique antigen presenting cells (APC) which play a pivotal role in immunotherapy and induction of an effective immune response against tumors. In the present study, 80% ethanol extract of Phyllanthus amarus was used to generate tumor lysate (TLY) derived from HCT 116 and MCF-7 cancer cell lines via induction of apoptosis. Monocyte-derived DCs were generated ex vivo from the adherent population of peripheral blood mononuclear cells (PBMCs). The generated TLY were used to impulse DCs to investigate its effect on their cellular immune functions including antigen presentation capacity, phagocytic activity, chemotaxis capacity, T-cell proliferation and cytokines release.
METHODS: The effect of P. amarus-generated TLY on DCs maturation was evaluated by determination of MHC class I, II and CD 11c expression as well as the co-stimulatory molecules CD 83 and 86 by using flow cytometry. The phagocytic capacity of TLY-pulsed DCs was investigated through FITC-dextran uptake by using flow cytometry. The effect on the cytokines release including IL-12, IL-6 and IL-10 was elucidated by using ELISA. The migration capacity and T cell proliferation activity of pulsed DCs were measured. The relative gene expression levels of cytokines were determined by using qRT-PCR. The major constituents of P. amarus extract were qualitatively and quantitatively analyzed by using validated reversed-phase high performance liquid chromatography (HPLC) methods.
RESULTS: P. amarus-generated TLY significantly up-regulated the expression levels of MHC class I, CD 11 c, CD 83 and 86 in pulsed DCs. The release of interleukin IL-12 and IL-6 was enhanced by TLY-DCs at a ratio of 1 DC: 3 tumor apoptotic bodies (APO), however, the release of IL-10 was suppressed. The migration ability as well as allogeneic T-cell proliferation activities of loaded DCs were significantly enhanced, but their phagocytic capacity was highly attenuated. The gene expression profiles for IL-12 and IL-6 of DCs showed increase in their mRNA gene expression in TLY pulsed DCs versus unloaded and LPS-treated only DCs.
CONCLUSION: The effect of P. amarus-generated TLY on the immune effector mechanisms of DCs verified its potential to induce an in vitro anti-tumor immune response against the recognized tumor antigen.

Matched MeSH terms: Phagocytosis/drug effects
Fulltext Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients

Mohd Idrus FN, Ahmad NS, Hoe CH, Azlan M, Norfuad FA, Yusof Z, et al.

BMC Immunol, 2021 03 24;22(1):21.
PMID: 33761885 DOI: 10.1186/s12865-021-00410-2

BACKGROUND: Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Higher expression of Mer proto-oncogene tyrosine kinase (MerTK) on M2 macrophage helps in maintaining macrophage efferocytic efficiency. In healthy individuals, macrophage polarization into M1 and M2 occurs in tissues in concomitance with the acquisition of functional phenotypes depending on specific microenvironment stimuli. However, whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown.
OBJECTIVE: This study aimed to elucidate the polarization of M1 and M2 macrophage from CAD patients as well as to investigate the expression of MerTK in these macrophage phenotypes.
METHODS: A total of 14 (n) CAD patients were recruited and subsequently grouped into "no apparent CAD", "non-obstructive CAD" and "obstructive CAD" according to the degree of stenosis. Thirty ml of venous blood was withdrawn to obtain monocyte from the patients. The M1 macrophage was generated by treating the monocyte with GMCSF, LPS and IFN-γ while MCSF, IL-4 and IL-13 were employed to differentiate monocyte into M2 macrophage. After 7 days of polarization, analysis of cell surface differentiation markers (CD86+/CD80+ for M1 and CD206+/CD200R+ for M2) and measurement of MerTK expression were performed using flow cytometry.
RESULTS: Both M1 and M2 macrophage expressed similar level of CD86, CD80 and CD206 in all groups of CAD patients. MerTK expression in no apparent CAD patients was significantly higher in M2 macrophage compared to M1 macrophage [12.58 ± 4.40 vs. 6.58 ± 1.37, p = 0.040].
CONCLUSION: Differential polarization of macrophage into M1 and M2 was highly dynamic and can be varied due to the microenvironment stimuli in atherosclerotic plaque. Besides, higher expression of MerTK in patients with the least coronary obstructive suggest its vital involvement in efferocytosis.

Matched MeSH terms: Phagocytosis
Effects of aqueous plant extracts on the phagocytic capability and intracellular killing of Staphyococcus aureus by murine peritoneal macrophages in vitro

Mahmood AA, Khiarul Anwar A, Ansary A, Sidik K, Salmah I, Suzainur KAR

JUMMEC, 2001;6:30-33.

Nine local plant species were picked randomly and their aqueous extracts have been screened to know their effects on the phagocytic capability and intracellular killing of StapllylococclIs al/rellS bacteria by mouse peritoneal macrophages. Macrophage cultures were incubated with different concentration of each plant extracts forI hour. Among these aqueous extracts, Ageratum conyzoides and Malastoma melabathricum inhibited the phagocytic capability and intracellular killing of Stapllylococclls aureus compared with controls. Elicited (activated) cells have more phagocytic capability and intracellular killing than the resident (normal) macrophages. There were no differences in the viability of cells between treated cells (with extracts) and controls (without extracts). KEYWORDS: Aqueous plant extracts, murine macrophage, phagocytosis.

Matched MeSH terms: Phagocytosis
Enhanced phagocytosis of Aggregatibacter actinomycetemcomitans cells by macrophages activated by a probiotic Lactobacillus strain

Jaffar N, Okinaga T, Nishihara T, Maeda T

J Dairy Sci, 2018 Jul;101(7):5789-5798.
PMID: 29680655 DOI: 10.3168/jds.2017-14355

The activation of phagocytosis is one important approach to clearing pathogenic cells in a host. This study evaluated the ability of probiotic lactobacilli to induce phagocytic activity as well as the clearance of a periodontal pathogen, Aggregatibacter actinomycetemcomitans. First, the activation of phagocytosis was found by using lyophilized dead cells. Probiotic Lactobacillus strains significantly enhanced the phagocytic activity of macrophage cells, indicating that the probiotic lactobacilli have a remarkable ability to stimulate the macrophages. Essentially, 3 Lactobacillus strains tested did not have any critical toxic effect on the murine macrophage, and Lactobacillus johnsonii NBRC 13952 showed the least cytotoxic effect on the RAW264.7 macrophages. The expression of classically activated macrophage markers, IL-1β, and cluster of differentiation 80 increased by L. johnsonii NBRC 13952; however, there was no significant difference for IL-18. The highest phagocytic activity by macrophages was found in a condition in which the macrophage activated by L. johnsonii NBRC 13952 functions to kill the cells of A. actinomycetemcomitans. Correlating with the result, a high amount of hypodiploid DNA (SubG1) was detected from the macrophage cells stimulated by L. johnsonii NBRC 13952. Taken together, the results suggest that macrophages activated by the Lactobacillus strain can facilitate the phagocytosis of A. actinomycetemcomitans cells by linking with enhanced apoptotic activities. In conclusion, L. johnsonii NBRC 13952 has a certain role in activating the RAW264.7 macrophages, thereby counteracting the infection of A. actinomycetemcomitans.

Matched MeSH terms: Phagocytosis
Fulltext Evaluation of phytoestrogens in inducing cell death mediated by decreasing Annexin A1 in Annexin A1-knockdown leukemia cells

Hasan M, Kumolosasi E, Jasamai M, Jamal JA, Azmi N, Rajab NF

Daru, 2020 Jun;28(1):97-108.
PMID: 31912375 DOI: 10.1007/s40199-019-00320-0

BACKGROUND: Phytoestrogens are plant compounds that are structurally similar to estrogen and that possess anti-cancer properties. Previous studies have reported that coumestrol, daidzein and genistein could induce cell death by reducing Annexin A1 protein in leukemic cell lines. Annexin A1 (ANXA1) is involved in cell progression, metastasis, and apoptosis in several types of cancer cells. The present study sought to investigate if the effects of phytoestrogens on apoptosis, cell cycle arrest and phagocytosis in ANXA1-knockdown leukemic cells are mediated through ANXA1 or occurred independently.
METHODS: Transfection of ANXA1 siRNA was conducted to downregulate ANXA1 expression in Jurkat, K562 and U937 cells. Apoptosis and cell cycle assays were conducted using flow cytometry. Western blot was performed to evaluate ANXA1, caspases and Bcl-2 proteins expression. Phagocytosis was determined using hematoxylin and eosin staining.
RESULTS: The expression of ANXA1 after the knockdown was significantly downregulated in all cell lines. Genistein significantly induced apoptosis associated with an upregulation of procaspase-3, -9, and - 1 in Jurkat cells. The Bcl-2 expression showed no significant difference in Jurkat, K562 and U937 cells. Treatment with phytoestrogens increased procaspase-1 expression in Jurkat and U937 cells while no changes were detected in K562 cells. Flow cytometry analysis demonstrated that after ANXA1 knockdown, coumestrol and genistein caused cell cycle arrest at G2/M phase in selected type of cells. The percentage of phagocytosis and phagocytosis index increased after the treatment with phytoestrogens in all cell lines.
CONCLUSION: Phytoestrogens induced cell death in ANXA1-knockdown leukemia cells, mediated by Annexin A1 proteins. Graphical abstract.

Matched MeSH terms: Phagocytosis/drug effects
Evaluation of variable parameters in neutrophil function test using chemiluminescence assay

Noah RM, Jais MR, Noh LM

Malays J Pathol, 1994 Dec;16(2):157-60.
PMID: 9053565

Variable parameters in chemiluminescence assay, one of the methods used to assess the functional capacity of neutrophils, were evaluated for suitable adaptation locally. The use of pooled normal human serum as compared to single normal human serum in opsonizing particles for phagocytosis was found to exhibit lower chemiluminescence activity (reduction range of 30%-50%). A similar degree of depression was observed when the particles were opsonized using normal human serum in comparison to that using autologous serum. Different intensity of chemiluminescence was also noted when the opsonized particle used was the Oxford strain of Staphylococcus aureus (NCTC 6571) in contrast to a strain of Staphylococcus aureus isolated from a patient. The results obtained warrant clinicians to deliver appropriate samples as best they can when the chemiluminescence assay is requested.

Matched MeSH terms: Phagocytosis/physiology*
Fulltext Factors influencing phagocytosis of malaria parasites: the story so far

Chua CLL, Ng IMJ, Yap BJM, Teo A

Malar J, 2021 Jul 16;20(1):319.
PMID: 34271941 DOI: 10.1186/s12936-021-03849-1

There are seven known species of Plasmodium spp. that can infect humans. The human host can mount a complex network of immunological responses to fight infection and one of these immune functions is phagocytosis. Effective and timely phagocytosis of parasites, accompanied by the activation of a regulated inflammatory response, is beneficial for parasite clearance. Functional studies have identified specific opsonins, particularly antibodies and distinct phagocyte sub-populations that are associated with clinical protection against malaria. In addition, cellular and molecular studies have enhanced the understanding of the immunological pathways and outcomes following phagocytosis of malaria parasites. In this review, an integrated view of the factors that can affect phagocytosis of infected erythrocytes and parasite components, the immunological consequences and their association with clinical protection against Plasmodium spp. infection is provided. Several red blood cell disorders and co-infections, and drugs that can influence phagocytic capability during malaria are also discussed. It is hoped that an enhanced understanding of this immunological process can benefit the design of new therapeutics and vaccines to combat this infectious disease.

Matched MeSH terms: Phagocytosis*
Flavonoids of Artocarpus heterophyllus Lam. heartwood inhibit the innate immune responses of human phagocytes

Septama AW, Jantan I, Panichayupakaranant P

J Pharm Pharmacol, 2018 Sep;70(9):1242-1252.
PMID: 29943393 DOI: 10.1111/jphp.12952

OBJECTIVES: To investigate the effects of flavonoids isolated from Artocarpus heterophyllus. heartwood on chemotaxis, phagocytosis, reactive oxygen species (ROS) production and myeloperoxidase (MPO) activity of human phagocytes.
METHODS: Chemotaxis was evaluated using a modified Boyden chamber and phagocytosis was determined by flowcytometer. Respiratory burst was investigated by luminol-based chemiluminescence assay while MPO activity was determined by colorimetric assay.
KEY FINDINGS: Artocarpanone and artocarpin strongly inhibited all steps of phagocytosis. Artocarpanone and artocarpin showed strong chemotactic activity with IC50 values of 6.96 and 6.10 μm, respectively, which were lower than that of ibuprofen (7.37 μm). Artocarpanone was the most potent compound in inhibiting ROS production of polymorphonuclear leucocytes and monocytes with IC50 values comparable to those of aspirin. Artocarpin at 100 μg/ml inhibited phagocytosis of opsonized bacteria (28.3%). It also strongly inhibited MPO release with an IC50 value (23.3 μm) lower than that of indomethacin (69 μm). Structure-activity analysis indicated that the number of hydroxyl group, the presence of prenyl group and variation of C-2 and C-3 bonds might contribute towards their phagocytosis.
CONCLUSIONS: Artocarpanone and artocarpin were able to suppress strongly the phagocytosis of human phagocytes at different steps and have potential to be developed into potent anti-inflammatory agents.

Matched MeSH terms: Phagocytosis/drug effects; Phagocytosis/immunology
Haemophagocytosis in dengue haemorrhagic fever: a case report

Ramanathan M, Duraisamy G

Ann Acad Med Singap, 1991 Nov;20(6):803-4.
PMID: 1803975

Virus associated haemophagocytic syndrome (VAHS), a distinct clinico-pathologic entity, is characterised by systemic proliferation of non-neoplastic histotiocytes showing haemophagocytosis resulting in blood cytopaenia. It has been described in relation to several viruses earlier. Here we describe a young girl who developed this reactive process during the course of dengue haemorrhagic fever (DHF).

Matched MeSH terms: Phagocytosis

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