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Sex-specific NLRP3 activation in neutrophils promotes neutrophil recruitment and NETosis in the murine model of diffuse alveolar hemorrhage
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Sex-specific NLRP3 activation in neutrophils promotes neutrophil recruitment and NETosis in the murine model of diffuse alveolar hemorrhage
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Sex-specific NLRP3 activation in neutrophils promotes neutrophil recruitment and NETosis in the murine model of diffuse alveolar hemorrhage
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Journal Article
Sex-specific NLRP3 activation in neutrophils promotes neutrophil recruitment and NETosis in the murine model of diffuse alveolar hemorrhage
2024
Overview
Objectives: Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus and small vessel vasculitis. We previously showed that neutrophil extracellular traps (NETs) were associated with the pathogenesis of pristane-induced DAH and demonstrated that neutrophil NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly participated in NET generation under sterile stimulation. We investigated whether NLRP3 inflammasome assembly in neutrophils may drive pulmonary NETosis in a mouse model of pristane-induced DAH.Methods: C57BL/6J mice received a single intraperitoneal injection of 0.5mL of pristane. Neutrophil NLRP3 inflammasome assembly and NETs were characterized by immunofluorescence staining of apoptosis-associated specklike protein a CARD (ASC), co-staining of DNA, and citrullinated histones, respectively. Clinical status of mice was assessed 11 days after pristane injection by measurement of arterial oxygen saturation and of weight loss; severity of lung injury was determined using a quantification score from hematoxylin-eosin-stained slides.Results: Pristane induced ASC speck formation in neutrophils and we confirmed that NLRP3 inflammasome was involved in NET generation after pristane stimulation in vitro. NLRP3 deficiency reduced the severity of pristaneinduced DAH in female, but not male mice. Interestingly, NLRP3 deficiency Frontiers in Immunology frontiersin.org 01
Publisher
CCSD,Frontiers,Frontiers Media SA,Frontiers Media S.A
Subject
/ Animals
/ Blood
/ Extracellular Traps - immunology
/ Extracellular Traps - metabolism
/ Female
/ Females
/ Histones
/ Lungs
/ Lupus
/ Male
/ Males
/ Mice
/ neutrophil extracellular traps
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Pristane
/ Pulmonary Alveoli - immunology
/ Pulmonary Alveoli - metabolism
/ Pulmonary Alveoli - pathology
/ Systemic lupus erythematosus
/ Terpenes
ISBN
9780013721970, 0013721976
