| Autor: |
Saeko Fukui, Shoichi Fukui, Stijn Van Bruggen, Lai Shi, Casey E. Sheehy, Long Chu, Denisa D. Wagner |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 12, Iss 1, Pp 1-9 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-022-25176-4 |
| Popis: |
Abstract NLR family pyrin domain containing 3 (NLRP3) inflammasome mediates caspase-1-dependent processing of inflammatory cytokines such as IL-1β, an essential endothelial activator, and contributes to the pathology of inflammatory diseases. To evaluate the role of NLRP3 in neutrophils in endothelial activation, which is still elusive, we used the thioglycollate-induced peritonitis model characterized by an early neutrophil influx, on Nlrp3 −/− and Nlrp3 +/+ mice. Nlrp3 −/− mice recruited fewer neutrophils than Nlrp3 +/+ into the peritoneum and showed lower IL-1β in peritoneal lavage fluid. The higher production of IL-1β in Nlrp3 +/+ was neutrophil-dependent as neutrophil depletion prevented the IL-1β production. The Nlrp3 +/+ neutrophils collected from the peritoneal fluid formed significantly more filaments (specks) than Nlrp3 −/− neutrophils of ASC (apoptosis-associated speck-like protein containing a caspase activating and recruitment domain), a readout for inflammasome activation. Intravital microscopy revealed that leukocytes rolled significantly slower in Nlrp3 +/+ venules than in Nlrp3 −/− . Nlrp3 −/− endothelial cells isolated from mesenteric vessels demonstrated a lower percentage of P-selectin-positive cells with lower intensity of surface P-selectin expression than the Nlrp3 +/+ endothelial cells evaluated by flow cytometry. We conclude that neutrophils orchestrate acute thioglycollate-induced peritonitis by producing IL-1β in an NLRP3-dependent manner. This increases endothelial P-selectin expression and leukocyte transmigration. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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