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Fulltext Reduction in Absolute Neutrophil Counts in Patient on Clozapine Infected with COVID-19

Ramli FF, Ali A, Syed Hashim SA, Kamisah Y, Ibrahim N

Int J Environ Res Public Health, 2021 10 27;18(21).
PMID: 34769806 DOI: 10.3390/ijerph182111289

Despite its severe adverse effects, such as agranulocytosis, clozapine is the primary treatment for treatment-resistant schizophrenia. The established clozapine monitoring system has contributed to reducing agranulocytosis incidence and mortality rates. However, the pandemic coronavirus disease 2019 (COVID-19) has caused changes in the monitoring system. This review aimed to assess the current evidence on the neutrophil changes in the patient on clozapine treatment and infected with COVID-19. Individual cases reported various absolute neutrophil count (ANC) levels, normal, reduced, or elevated. No agranulocytosis case was reported. One case had a borderline moderate-severe ANC level, but the patient was in the 18-week period of clozapine treatment. A cumulative analysis of case the series initially reported inconclusive results. However, a more recent study with a larger sample size reported a significant reduction in the ANC during COVID-19 infection. Nevertheless, this effect is transient as no significant difference was found between the baseline and the post-infection period in ANC levels. In conclusion, COVID-19 is associated with a temporary reduction in ANC levels. The results supported the recommendation to reduce the frequency of clozapine monitoring in the eligible candidates. However, more data are required to confirm the current findings given the limitations, including study design, sample size, and statistical analysis.

Matched MeSH terms: Neutrophils
Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, and platelet-lymphocyte ratio in stroke-associated pneumonia: a systematic review and meta-analysis

Zawiah M, Hayat Khan A, Abu Farha R, Usman A, Bitar AN

Curr Med Res Opin, 2023 Mar;39(3):475-482.
PMID: 36710633 DOI: 10.1080/03007995.2023.2174327

BACKGROUND: Predicting stroke-associated pneumonia (SAP) is crucial for intensifying preventive measures and decreasing morbidity and mortality. This meta-analysis aims to evaluate the association between baseline neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) with SAP and to determine the strength of the association.
METHODS: The Web of Science, SCOPUS, and PUBMED databases were searched to find eligible studies. The standardized mean difference (SMD) and 95% confidence interval (CI) were used to evaluate the differences in NLR, MLR, and PLR levels between SAP and non-SAP patients. The meta-analysis was conducted using the software "Review Manager" (RevMan, version 5.4.1, September 2020). The random-effect model was used for the pooling analysis if there was substantial heterogeneity. Otherwise, the fixed-effect model was adopted.
RESULTS: Twelve studies comprising 6302 stroke patients were included. The pooled analyses revealed that patients with SAP had significantly higher levels of NLR, MLR, and PLR than the non-SAP group. The SMD, 95% CI, p-value, and I2 for them were respectively reported as (0.88, 0.70-1.07, .00001, 77%); (0.94, 0.43-1.46, .0003, 93%); and (0.61, 0.47-0.75, .001, 0%). Subgroup analysis of NLR studies showed no significant differences in the effect size index between the severity of the stroke, the sample size, and the period between the stroke onset and the blood sampling.
CONCLUSION: This systematic review and meta-analysis suggest that an elevated NLR, MLR, and PLR were associated with SAP, indicating that they could be promising blood-based biomarkers for predicting SAP. Large-scale prospective studies from various ethnicities are recommended to validate this association before they can be applied in clinical practice.

Matched MeSH terms: Neutrophils*
Fulltext Optimisation of laboratory procedures for isolating human peripheral blood derived neutrophils

Maqbool M, Vidyadaran S, George E, Ramasamy R

Med J Malaysia, 2011 Oct;66(4):296-9.
PMID: 22299545 MyJurnal

Functional analysis of neutrophils requires isolation of these cells in the laboratory. Current isolation procedures are time consuming and can potentially activate the resting neutrophils. Thus, in this present study, we have optimised an existing laboratory protocol for human neutrophil isolation from peripheral blood. Twenty ml of blood samples were subjected to optimised density gradient separation and dextran sedimentation to obtain a pure population of neutrophils. The efficacy of the optimised manual post isolation of neutrophils was compared with pre isolation count performed by an automated haematology analyzer. The recovery of neutrophils via our optimised methods was 65.5% in comparison with neutrophils counts at pre-isolation. The morphological analysis of isolated neutrophils indicated the purity level more than 95% using Leishman staining. Our optimised laboratory procedures for neutrophils isolation successfully harvested neutrophils with good viability, purity and post recovery yield. This procedure provides an ideal platform to separate neutrophils for in vitro studies.

Matched MeSH terms: Neutrophils/cytology*
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: Neutrophils/physiology*
Fulltext Maternal and umbilical cord blood polymorphonuclear leukocytes showed moderate oxidative burst at phagocytosis of Gardnerella vaginalis

Swaminathan A, Abd Aziz NH, Ayub NA, Wong KK, Cheah FC

BMC Res Notes, 2021 Nov 22;14(1):420.
PMID: 34809696 DOI: 10.1186/s13104-021-05842-y

OBJECTIVE: Pregnant women with bacterial vaginosis due to Gardnerella vaginalis (GV) infection presents with a wide-ranging disease symptomatology. We speculate this may be due to interaction that varies between host immune response and the pathogen. We studied the oxidative burst in polymorphonuclear leukocytes (PMNL)s from maternal blood (MB) and cord blood (CB) upon phagocytosis of GV and compared against E. coli and Group B Streptococcus (GBS).
RESULTS: The PHAGOBURST™ assay detects fluorescence from oxidized dihydrorhodamine during oxidative burst. The average percentage of PMNL showing oxidative burst was almost two-fold greater with GBS (99.5%) and E. coli (98.2%) than GV (56.9%) (p

Matched MeSH terms: Neutrophils*
Abnormality of polymorphonuclear leukocyte candidacidal activity in children with atopic dermatitis

Noah, R.M., Chin, K.T., Sulaiman, S., Jais, M.R.

Malaysian Journal of Child Health, 1998;10(1):72-77.
MyJurnal

Candidacidal assay was used to assess the phagocytic and killing activities of polymorphonuclear leukocytes from paediatric patients diagnosed to manifest with characteristics of atopic dermatitis. From this group of patients evaluated, all the 11 cases exhibited lower candidacidal activity in comparison to the normal children. However, there were no abnormalities observed in the engulfing abilities and myeloperoxidase activities of these leukocytes. The result indicated that lower killing capacity of polymorphonuclear leukocytes in these patients may contribute to the frequent bacterial infections in atopic dermatitis children.

Matched MeSH terms: Neutrophils
Predictors of stroke-associated pneumonia and the predictive value of neutrophil percentage-to-albumin ratio

Zawiah M, Khan AH, Abu Farha R, Usman A, AbuHammour K, Abdeen M, et al.

Postgrad Med, 2023 Sep;135(7):681-689.
PMID: 37756038 DOI: 10.1080/00325481.2023.2261354

BACKGROUND: Early recognition of stroke-associated pneumonia (SAP) is critical to reducing morbidity and mortality associated with SAP. This study investigated the predictors of SAP, and the predictive value of the neutrophil percentage-to-albumin ratio (NPAR) for SAP.
METHODS: This retrospective cohort study was conducted among stroke patients admitted to Jordan University Hospital from January 2015 to May 2021. Multivariable logistic regression was used to identify independent predictors for SAP. The predictive performance was assessed using C-statistics, described as the area under the receiver-operating characteristic curve (AUC, ROC) with a 95% confidence interval.
RESULTS: Four hundred and six patients were included in the analysis, and the prevalence of SAP was 19.7%. Multivariable logistic analysis showed that males (Adjusted Odds Ratio (AOR): 5.74; 95% Confidence Interval (95%CI): 2.04-1 6.1)], dysphagia (AOR: 5.29; 95% CI: 1.80-15.5), hemiparesis (AOR: 3.27; 95% CI: 1.13-9.47), lower GCS score (AOR: 0.73; 95% CI: 0.58-0.91), higher levels of neutrophil-lymphocyte ratio (NLR) (AOR: 1.15; 95% CI: 1.07-1.24), monocyte-lymphocyte ratio (MLR) (AOR: 1.49; 95% CI: 1.13-1.96), and neutrophil percentage to albumin ratio (NPAR) (AOR: 1.53; 95% CI: 1.33-1.76) were independent predictors of SAP. The NPAR demonstrated a significantly higher AUC than both the NLR (0.939 versus 0.865, Z = 3.169, p = 0.002) and MLR (0.939 versus 0.842, Z = 3.940, p

Matched MeSH terms: Neutrophils
Elevated neutrophil respiratory burst activity in essential hypertensive patients

Ramasamy R, Maqbool M, Mohamed AL, Noah RM

Cell Immunol, 2010;263(2):230-4.
PMID: 20471005 DOI: 10.1016/j.cellimm.2010.04.004

Neutrophils play a significant role in maintaining the integrity of innate immunity via their potent respiratory burst activity. However, the uncontrolled activation of respiratory burst in neutrophils also attributes to chronic diseases such as primary hypertension and atherosclerosis. In our study, we have investigated the activation of respiratory burst function of neutrophils harvested from essential hypertensive patients. In the presence of stimuli PMA and opsonized zymosan (OZ), hypertensive patients' neutrophils secrete significantly higher amount of superoxide anions compared to normotensive control. Although the magnitude of activation varies between both groups, yet the kinetics of activation is similar. When normotensive control's neutrophils were pre-treated with hypertensive serum, the cells failed to migrate toward fMLP which indicates the impairment of the migration property. In conclusion, the respiratory burst activity of neutrophils is affected by hypertension and their elevated superoxide anions production could be an aggravating factor in hypertension-related complication.

Matched MeSH terms: Neutrophils/immunology*
Fulltext Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer

Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH, et al.

Br. J. Cancer, 2015 Jun 30;113(1):150-8.
PMID: 26022929 DOI: 10.1038/bjc.2015.183

Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.

Matched MeSH terms: Neutrophils/pathology*
Fulltext Comparison of three different methods in the assessment of neutrophil function

Noah RM, Jais MR, Noh LM

Med J Malaysia, 1995 Jun;50(2):136-40.
PMID: 7565182

Three different methods to measure the oxidative respiratory burst of neutrophils were performed. Of the three, the chemiluminescence technique was observed to be the most sensitive among them. The strong statistical correlation and an acceptable agreement between chemiluminescence with that of the killing assay provides evidence for using the chemiluminescence assay as an alternative method of detecting gross defects of neutrophil respiratory burst killing assays.

Matched MeSH terms: Neutrophils/physiology*
Fulltext Erythema nodosum leprosum in Malaysians

Jayalakshmi P, Ganesapillai T, Ganesan J

Int. J. Lepr. Other Mycobact. Dis., 1995 Mar;63(1):109-11.
PMID: 7730709
Matched MeSH terms: Neutrophils/pathology
Human neutrophil antigen frequency data for Malays, Chinese and Indians

Hajar CGN, Zulkafli Z, Md Riffin NS, Tuan Mohammad TH, Safuan S, Nelson BR, et al.

Transfus Apher Sci, 2020 Apr;59(2):102651.
PMID: 31606336 DOI: 10.1016/j.transci.2019.09.004

BACKGROUND: Human neutrophil antigens (HNAs) are implicated in several clinical disorders and their allelic variations have been reported for many populations. This new study was aimed to report the genotype and alleles frequencies of HNA-1, -3, -4 and -5 loci in Malays, Chinese and Indians in Peninsular Malaysia.
METHODS: A total of 222 blood samples were collected from healthy, unrelated Malay, Chinese and Indian individuals. Their HNA-1, -3 and -4 and HNA-5 loci were genotyped using polymerase chain reaction-sequence specific primer (PCR-SSP) or PCR-restriction fragment length polymorphism (RFLP) assays.
RESULTS: All HNA loci are polymorphic, except for HNA -4. Geneotypes HNA-1a/1b, -3a/3b and -4a/4a were observed most frequently at these three loci in all three ethnic groups. In contrast, HNA-5a/5b and -5a/5a were observed as the predominant genotypes in Malays vs. Chinese and Indians, respectively. The Malays, Chinese and Indians shared HNA -3a (0.505-0.527), HNA -4a (1.000) and -5a (0.676-0.854) as the most frequent alleles. However, HNA-1a was found to be the most common in Malays (0.506) and Chinese (0.504) and HNA-1b for Indians (0.525).
CONCLUSION: Combined with HNA data that have been published for Malay subethnic and Orang Asli groups, this study provides the first fully comprehensive HNA dataset for populations to be found in Peninsular Malaysia. Overall, our findings provide further evidence of genetic complexity in the region. This now publicly available HNA dataset can be used as a reliable reference source for improving medical outcomes.

Matched MeSH terms: Neutrophils/immunology*
Lack of neutrophil degranulation in low-dose endotoxin inhalation based on a novel intracellular assay

Loh LC, Lo WH, Kanabar V, O'Connor BJ

Asian Pac J Allergy Immunol, 2006 Jun-Sep;24(2-3):153-60.
PMID: 17136881

To study the nature of endotoxin or lipopolysaccharide (LPS) induced inflammation, we developed a method of quantifying intracellular human neutrophil elastase (HNE) in lysed sputum polymorphs as a means to study the degranulation status of LPS-recruited neutrophils. Induced sputum, blood and exhaled nitric oxide (NO) were collected from 10 healthy non-atopic human subjects after inhaling a single 15 microg dose of Escherichia coil LPS in an open study. At 6 hours, LPS inhalation caused significant increase of sputum and blood neutrophils but without parallel increase in myeloperoxidase, HNE or interleukin-8 (IL-8) in sputum sol and blood, or exhaled NO. Intracellular HNE in lysed sputum polymorphs or purified blood neutrophils did not show any significant changes between inhaled LPS and saline, nor was there any appreciable change in percentage HNE release induced by N-Formyl-Met-Leu-Phe (fMLP) in vitro. We concluded that in healthy humans, the transient neutrophilic inflammation induced by a single dose of inhaled 15 microg LPS is mainly characterized by cell recruitment, not enhanced secretion of granular mediators or increased exhaled NO based on our experimental conditions.

Matched MeSH terms: Neutrophils/drug effects; Neutrophils/enzymology; Neutrophils/physiology*
Fulltext Polymorph identification studies on cocoa butter from Sabah

Nur Fadzilah Basri, Fauziah Abdul Aziz, Mohd Omar, A.K., Nik Norulaini, A.R.

Journal of Nuclear and Related Technologies, 2009;2009(1):159-164.
MyJurnal

The main purpose of this study was to analyzed and examined the cocoa butter samples from Sabah. This work presence the crystal phases present in cocoa butter sample thus proved the existence of polymorphs obtained from differential scanning calorimeter (DSC) analysis and confirmed by X-ray diffraction (XRD). The cocoa butter samples were extracted using a conventional method by Soxhlet Extraction method. Crystals were formed under controlled static and tempered conditions. Cocoa butter polymorphism demonstrates that it is the actual crystallization temperature, not the cooling rate that determines the polymorph that crystallizes.

Matched MeSH terms: Neutrophils
Fulltext Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1hi neutrophil in myocardial ischemia-reperfusion injury

Dong Y, Kang Z, Zhang Z, Zhang Y, Zhou H, Liu Y, et al.

Sci Bull (Beijing), 2024 Apr 15;69(7):949-967.
PMID: 38395651 DOI: 10.1016/j.scib.2024.02.003

Myocardial ischemia-reperfusion injury (MIRI) is a major hindrance to the success of cardiac reperfusion therapy. Although increased neutrophil infiltration is a hallmark of MIRI, the subtypes and alterations of neutrophils in this process remain unclear. Here, we performed single-cell sequencing of cardiac CD45+ cells isolated from the murine myocardium subjected to MIRI at six-time points. We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI. Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations, including Ccl3hi Neu and Ym-1hi Neu, which were increased at 6 h and 1 d after reperfusion, respectively. Ym-1hi Neu selectively expressed genes with protective effects and was, therefore, identified as a novel specific type of cardiac cell in the injured heart. Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues, especially instructing the response of macrophages. The abundance of Ym-1hi Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D (Ly6G) or anti-Intercellular cell adhesion molecule-1 (ICAM-1) neutralizing antibodies. In addition, a neutrophil subtype with the same phenotype as Ym-1hi Neu was detected in clinical samples and correlated with prognosis. Ym-1 inhibition exacerbated myocardial injury, whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice, which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue. Overall, our findings reveal the anti-inflammatory phenotype of Ym-1hi Neu and highlight its critical role in myocardial protection during the early stages of MIRI.

Matched MeSH terms: Neutrophils
Defining a pro-inflammatory neutrophil phenotype in response to schistosome eggs

Chuah C, Jones MK, Burke ML, McManus DP, Owen HC, Gobert GN

Cell. Microbiol., 2014 Nov;16(11):1666-77.
PMID: 24898449 DOI: 10.1111/cmi.12316

Neutrophils contribute to the pathological processes of a number of inflammatory disorders, including rheumatoid arthritis, sepsis and cystic fibrosis. Neutrophils also play prominent roles in schistosomiasis japonica liver fibrosis, being central mediators of inflammation following granuloma formation. In this study, we investigated the interaction between Schistosoma japonicum eggs and neutrophils, and the effect of eggs on the inflammatory phenotype of neutrophils. Our results showed significant upregulated expression of pro-inflammatory cytokines (IL-1α, IL-1β and IL-8) and chemokines (CCL3, CCL4 and CXCL2) in neutrophils after 4 h in vitro stimulation with S. japonicum eggs. Furthermore, mitochondrial DNA was released by stimulated neutrophils, and induced the production of matrix metalloproteinase 9 (MMP-9), a protease involved in inflammation and associated tissue destruction. We also found that intact live eggs and isolated soluble egg antigen (SEA) triggered the release of neutrophil extracellular traps (NETs), but, unlike those reported in bacterial or fungal infection, NETs did not kill schistosome eggs in vitro. Together these show that S. japonicum eggs can induce the inflammatory phenotype of neutrophils, and further our understanding of the host-parasite interplay that takes place within the in vivo microenvironment of schistosome-induced granuloma. These findings represent novel findings in a metazoan parasite, and confirm characteristics of NETs that have until now, only been observed in response to protozoan pathogens.

Matched MeSH terms: Neutrophils/immunology*; Neutrophils/parasitology*
Immunosuppressive effects of the standardized extract of Zingiber zerumbet on innate immune responses in Wistar rats

Ghazalee NS, Jantan I, Arshad L, Haque MA

Phytother Res, 2019 Apr;33(4):929-938.
PMID: 30618097 DOI: 10.1002/ptr.6285

Zingiber zerumbet rhizome has been used in traditional medicine mainly for the treatment of various immune-inflammatory related ailments and has been shown to exhibit a wide spectrum of biological effects especially antioxidant and anti-inflammatory activities. The present study was aimed to investigate the immunosuppressive effects of the standardized 80% ethanol extract of Z. zerumbet at 100, 200, and 400 mg/kg on the innate immune responses in male Wistar rats. The immune parameters determined were chemotaxis of neutrophils, Mac-1 expression, engulfment of Escherichia coli by neutrophils, reactive oxygen species production, and plasma lysozyme and ceruloplasmin levels. Zerumbone was qualitatively and quantitatively determined in the extract by using a validated reversed-phase HPLC, whereas liquid chromatography tandem-mass spectrometry (LC -MS/MS) was used to profile the secondary metabolites. Z. zerumbet significantly inhibited the migration of neutrophils, expressions of CD11b/CD18 integrin, phagocytic activity, and production of reactive oxygen species in a dose-dependent manner. The extract also dose-dependently inhibited the expressions of lysozyme and ceruloplasmin in the rat plasma. Z. zerumbet extract possessed strong inhibitory effects on the innate immune responses and has potential to be developed into an effective immunosuppressive agent.

Matched MeSH terms: Neutrophils/drug effects; Neutrophils/immunology
Fulltext IL-36 Promotes Systemic IFN-I Responses in Severe Forms of Psoriasis

Catapano M, Vergnano M, Romano M, Mahil SK, Choon SE, Burden AD, et al.

J Invest Dermatol, 2020 04;140(4):816-826.e3.
PMID: 31539532 DOI: 10.1016/j.jid.2019.08.444

Psoriasis is an immune-mediated skin disorder associated with severe systemic comorbidities. Whereas IL-36 is a key disease driver, the pathogenic role of this cytokine has mainly been investigated in skin. Thus, its effects on systemic immunity and extracutaneous disease manifestations remain poorly understood. To address this issue, we investigated the consequences of excessive IL-36 activity in circulating immune cells. We initially focused our attention on generalized pustular psoriasis (GPP), a clinical variant associated with pervasive upregulation of IL-36 signaling. By undertaking blood and neutrophil RNA sequencing, we demonstrated that affected individuals display a prominent IFN-I signature, which correlates with abnormal IL-36 activity. We then validated the association between IL-36 deregulation and IFN-I over-expression in patients with severe psoriasis vulgaris (PV). We also found that the activation of IFN-I genes was associated with extracutaneous morbidity, in both GPP and PV. Finally, we undertook mechanistic experiments, demonstrating that IL-36 acts directly on plasmacytoid dendritic cells, where it potentiates toll-like receptor (TLR)-9 activation and IFN-α production. This effect was mediated by the upregulation of PLSCR1, a phospholipid scramblase mediating endosomal TLR-9 translocation. These findings identify an IL-36/ IFN-I axis contributing to extracutaneous inflammation in psoriasis.

Matched MeSH terms: Neutrophils/immunology; Neutrophils/metabolism
Human mesenchymal stem cells protect neutrophils from serum-deprived cell death

Maqbool M, Vidyadaran S, George E, Ramasamy R

Cell Biol Int, 2011 Dec;35(12):1247-51.
PMID: 21649586 DOI: 10.1042/CBI20110070

We have previously shown that human MSC (mesenchymal stem cells) inhibit the proliferation of most of the immune cells. However, there are innate immune cells such as neutrophils and other PMN (polymorphonuclear) cells that do not require an extensive proliferation prior to their effector function. In this study, the effect of MSC on neutrophils in the presence of complete and serum-deprived culture media was investigated. In the presence of MSC, the viability of neutrophils increase as measured in 24 h of incubation at various supplementation of serum concentration. We have utilized Annexin V and PI (propidium iodide) staining to confirm whether the enhancement of neutrophil's viability is due to a reduction in PCD (programmed cell death). MSC significantly rescue neutrophils from apoptosis at 1, 5 and 10% of FBS (fetal bovine serum) supplementation. The fractions of viable and dead cells were increased and decreased respectively in the presence of MSC. Our results indicate MSC rescue neutrophils from nutrient- or serum-deprived cell death. However, whether this effect is exerted through a specific signalling pathway or confining neutrophils in resting state by MSC requires further investigation.

Matched MeSH terms: Neutrophils/cytology*; Neutrophils/metabolism
Defective rapid cell shape and transendothelial migration by calpain-1 null neutrophils

Ishak R, Hallett MB

Biochem Biophys Res Commun, 2018 12 02;506(4):1065-1070.
PMID: 30409431 DOI: 10.1016/j.bbrc.2018.10.174

It has been proposed that Ca2+ activation of calpain-1 is an important trigger for rapid cell spreading by neutrophils. In this paper, we have investigated this by assessing the ex vivo functioning of neutrophils from calpain-1 null mice, Calpain-1 null neutrophils failed to migrate through TNF-activated endothelial monolayers. The failure to transmigrate through endothelial monolayers was therefore unlikely to be due to a failure of chemotaxis as chemotaxis by adherent calpain-1 null neutrophils towards fMLP was unpaired. In contrast, the capacity of calpian-1 neutrophils to spontaneously spread was limited to smaller diameters than for wild type cells. Photolytic uncaging of IP3 with Individual wild type neutrophils resulted in a large Ca2+ signal and rapid cell spreading. In contrast, calpain-1 neutrophils failed to spread in response to the IP3-induced Ca2+ signal. This work has therefore demonstrated that the presence of calpain-1 was required for effective rapid cell spreading by neutrophils.

Matched MeSH terms: Neutrophils/enzymology*; Neutrophils/pathology*

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