Platelet α‐granules modulate the inflammatory response under systemic lipopolysaccharide injection in mice

Abstract

BACKGROUND Beyond their role in hemostasis and thrombosis, platelets are also important mediators of inflammation by the release of hundreds of factors stored in their α‐granules. Mutations in Nbeal2 cause gray platelet syndrome (GPS), characterized by the lack of platelet α‐granules. This study aims to evaluate the immunological (proinflammatory) effects of platelet α‐granules. STUDY DESIGN AND METHODS We performed an experiment using Nbeal2−/− mice, the mouse model of GPS. Systemic inflammation was induced by intravenous injection of lipopolysaccharide (LPS). Inflammatory response was assessed by quantification of inflammatory soluble factors and platelet biological response modifiers. RESULTS The lack of Nbeal2 (in Nbeal2 −/− mice, compared with controls) significantly reduced the recruitment of circulating neutrophils and monocytes. Moreover, after LPS injection, there was a significant increase in neutrophil and monocyte counts in control animals, compared with Nbeal2 −/− mice. The control of inflammation, evaluated by the production of anti‐inflammatory cytokines, appeared to be greater in Nbeal2−/− mice compared with controls. Conversely, the production of certain inflammatory‐soluble mediators known to characterize normal platelet secretion, such as soluble CD40 ligand (sCD40L), was decreased under experimental inflammation in Nbeal2 −/− mice. CONCLUSIONS These results show that α‐granules play a direct role in platelet‐mediated inflammation balance, confirming the need to further investigate platelet‐associated inflammatory pathophysiology and inflammatory adverse events related to blood transfusion.

The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2–infected patients by sex and age

“…Female patients also exhibited reduced levels of IL-1 β when compared with male patients, a proinflammatory cytokine considered a potential target for COVID-19 therapy ( 34 ). Other proinflammatory transcripts (neurobeachin-like 2 [ NBEAL2 ]) critical for leukocyte recruitment and granule exocytosis ( 35 , 36 ) or alarmins that are released during tissue damage (S100 calcium binding protein A9 [ S100A9 ]) ( 37 , 38 ) were lower in swabs from female patients infected with SARS-CoV-2 in comparison with male patients. The differential expression analysis between female and male samples, both SARS-CoV-2–negative groups, showed downregulation of several genes belonging to the CMSP term ( Supplemental Figure 7, A and B ).…”

Specific immune-regulatory transcriptional signatures reveal sex and age differences in SARS-CoV-2 infected patients

“…Females also exhibited reduced levels of IL-1β when compared to male patients, a pro-inflammatory cytokine considered a potential target for COVID-19 therapy 27 . Other pro-inflammatory transcripts (neurobeachin like 2, NBEAL2 ) critical for leukocyte recruitment and granule exocytosis 28,29 or alarmins that are released during tissue damage (S100 Calcium Binding Protein A9, S100A9 ) 30,31 were lower in swabs from females infected with SARS-CoV-2 in comparison to males. Multivariate regression analysis indicated that the expression of genes shown in Fig.…”

Dynamics of Platelet Counts in Major Trauma: The Impact of Haemostatic Resuscitation and Effects of Platelet Transfusion—A Sub-Study of the Randomized Controlled RETIC Trial

“…Platelets (PLT) play a central role in haemostasis, and their role in modulating the inflammatory response is increasingly recognized [12][13][14][15]. PLT and fibrinogen are important substrates needed for clot formation.…”