In:
Cells, MDPI AG, Vol. 11, No. 23 ( 2022-12-06), p. 3944-
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.
Type of Medium:
Online Resource
ISSN:
2073-4409
DOI:
10.3390/cells11233944
Language:
English
Publisher:
MDPI AG
Publication Date:
2022
detail.hit.zdb_id:
2661518-6
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