IntroductionIn addition to their role in facilitating leukocyte-mediated inflammation, platelets can dampen leukocyte pro-inflammatory responses in some contexts. Consequently, platelets are increasingly appreciated as regulators of inflammation. Together, platelets and neutrophils play a role in inflammation through Toll-like receptor (TLR) expression, although we do not fully understand how platelets shape neutrophil responses to TLR stimulation. Here, we aimed to determine the extent to which platelets can modulate neutrophil function in response to in vitro stimulation with TLR4, TLR2/1, and TLR2/6 agonists.MethodsNeutrophils from 10 healthy individuals were cultured alone or with autologous platelets. Neutrophils ± platelets were left unstimulated or were stimulated with 1 or 100 ng/mL lipopolysaccharide (LPS; a TLR4 agonist), Pam3CSK4 (a TLR2/1 agonist) and fibroblast-stimulating lipopeptide (FSL)-1 (a TLR2/6 agonist). Neutrophil activation and phagocytic activity were assessed by flow cytometry, and elastase and interleukin-8 secretion were assessed by ELISA.ResultsThe addition of platelets attenuated neutrophil CD66b and CD11b expression in response to various doses of Pam3CSK4 and FSL-1. Furthermore, platelet co-culture was associated with higher CD62L expression (indicating reduced CD62L shedding) in response to these TLR agonists. Platelets also reduced elastase secretion in unstimulated cultures and in response to low-dose TLR stimulation. Conversely, platelet co-culture increased neutrophil phagocytosis in unstimulated cultures and in response to low-dose Pam3CSK4 and FSL-1. Platelets also increased IL-8 secretion in response to low-dose LPS.ConclusionPlatelets are complex immunomodulators that can attenuate some, and simultaneously augment other, neutrophil functions. This modulation can occur both in the absence and presence of TLR stimulation.

Aim: This study investigated an optimal extracellular matrix (ECM) biomarker panel for measurement in acute myocardial infarction (AMI). Materials & methods: Blood samples were collected from 12 healthy volunteers, and from 23 patients during hospital admission (day 1–3) and 6 months following AMI. Protein assays measured: FGFb, MMP-2, -3, -8, -9, osteopontin, periostin, PINP, TGF-β1, TIMP-1, -4 and VEGF. Results: When compared with healthy levels, seven ECM biomarkers were significantly altered in AMI patients, and six of these biomarkers displayed stable expression during hospital admission. Clinical characteristics and baseline cardiac function were not well correlated with ECM biomarkers. Conclusion: We suggest, MMP-2, MMP-3, MMP-8, MMP-9, periostin, PINP and TIMP-1 may be useful ECM biomarkers for future studies in AMI patients.