| First Author | Fukui S | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 21313 |
| PubMed ID | 36494392 | Mgi Jnum | J:334785 |
| Mgi Id | MGI:7410518 | Doi | 10.1038/s41598-022-25176-4 |
| Citation | Fukui S, et al. (2022) NLRP3 inflammasome activation in neutrophils directs early inflammatory response in murine peritonitis. Sci Rep 12(1):21313 |
| abstractText | NLR family pyrin domain containing 3 (NLRP3) inflammasome mediates caspase-1-dependent processing of inflammatory cytokines such as IL-1beta, 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-1beta in peritoneal lavage fluid. The higher production of IL-1beta in Nlrp3(+/+) was neutrophil-dependent as neutrophil depletion prevented the IL-1beta 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-1beta in an NLRP3-dependent manner. This increases endothelial P-selectin expression and leukocyte transmigration. |
