Role of S100A8/A9 in Platelet–Neutrophil Complex Formation during Acute Inflammation

Abstract

Acute respiratory distress syndrome (ARDS) due to pulmonary infections is associated with high morbidity and mortality. Upon inflammation, the alarmin S100A8/A9 is released and stimulates neutrophil recruitment mainly via binding to Toll-like receptor 4 (TLR4). TLR4 is also expressed on platelets, which modulate the immune response through direct interaction with leukocytes. In a murine model of Klebsiella pneumoniae-induced pulmonary inflammation, global S100A9 deficiency resulted in diminished neutrophil recruitment into the lung alveoli and neutrophil accumulation in the intravascular space, indicating an impaired neutrophil migration. A lack of TLR4 on platelets resulted in reduced neutrophil counts in the whole lung, emphasising the impact of TLR4-mediated platelet activity on neutrophil behaviour. Flow cytometry-based analysis indicated elevated numbers of platelet–neutrophil complexes in the blood of S100A9−/− mice. Intravital microscopy of the murine cremaster muscle confirmed these findings and further indicated a significant increase in neutrophil–platelet complex formation in S100A9−/− mice, which was reversed by administration of the S100A8/A9 tetramer. An in vitro bilayer assay simulated the murine alveolar capillary barrier during inflammation and validated significant differences in transmigration behaviour between wild-type and S100A9−/− neutrophils. This study demonstrates the role of S100A8/A9 during platelet–neutrophil interactions and neutrophil recruitment during pulmonary inflammation.

Serum Mrp 8/14 as a Potential Biomarker for Predicting the Occurrence of Acute Respiratory Distress Syndrome Induced by Sepsis: A Retrospective Controlled Study

“…22 Mrp 8/14, a protein linked to inflammatory responses, is released abundantly and actively participates in the recruitment of leukocytes and cytokine secretion upon infection, thereby exacerbating inflammatory responses and tissue damage. [23][24][25] In our study, we performed a preliminary experiment exploration and observed a clear detectable difference in the expression level of Mrp 8/14 between septic patients and ARDS patients, which is consistent with the previous study that serum Mrp 8/14 was significantly higher in ARDS and mechanical ventilation patients. 18 However, the higher expression level of Mrp 8/14 observed in our study may be attributed to the inclusion of ARDS patients with not only viral infections but also disease-causing microorganisms such as bacteria compared to the previous one.…”

Integrated multi-omics and artificial intelligence to explore new neutrophils clusters and potential biomarkers in sepsis with experimental validation

“…A previous study verified that expressions of S100A8/A9 are elevated in blood cells of sepsis patients and S100A8/A9 showed high accuracy in sepsis diagnosis ( 38 ). S100A8/A9 also interacted with platelets under inflammation and regulated neutrophil recruitment ( 39 ). S100A8/A9 bind to TLR-4 and induce platelet pyroptosis, which are highly effective in causing NETosis ( 40 ).…”

Is There a Difference in the Proteomic Profile of Stimulated and Unstimulated Saliva Samples from Pregnant Women with/without Obesity and Periodontitis?

“…Proteins S100-A8 and S100-A9 present proinflammatory, antimicrobial, oxidant-scaveng ing, and apoptosis-inducing activities. Their proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration [33][34][35]. Regarding Heat shock proteins (HSPs), they are associated with the body's metabolic and catabolic processes in addition to immune response and oxidative stress.…”