A self-organized actomyosin drives multiple intercellular junction disruption and directly promotes neutrophil recruitment in lipopolysaccharide-induced acute lung injury.

Abstract

Acute lung injury (ALI), with the hallmarks of vascular integrity disruption and neutrophil recruitment, is associated with high morbidity and mortality. Enhanced actomyosin assembly contributes to endothelial cell contact dysfunction. However, the roles and mechanisms of actomyosin assembly in ALI are not totally clear. We investigated the dynamic alterations and roles of actomyosin in ALI in vivo and in vitro models induced by LPS. Pulmonary levels of E-cadherin, vascular endothelial-cadherin, occludin, myosin phosphatase target subunit 1, and thymosin β4 were decreased, and the number and activity of neutrophils and the levels of actomyosin, p-ρ-associated protein kinase, p-myosin light-chain kinase, and profilin1 were increased within 3 d after LPS administration, and then, those alterations were recovered within the next 4 d, which was consistent with the alterations of lung histology, vascular permeability, edema, and serum levels of IL-6 and TNF-α. Direct or indirect inhibition of increased F-actin or myosin assembly ameliorated the reduction of intercellular junction molecules, the activation and migration of neutrophils, and the degree of lung injury. Moreover, neutrophil activation further promoted actomyosin assembly and aggravated lung injury. Conclusively, the enhancement of self-organized actomyosin contributes to alveolar-capillary barrier disruption and neutrophil recruitment in inflammatory response, which is a potential therapeutic target for ALI.-Chen, B., Yang, Z., Yang, C., Qin, W., Gu, J., Hu, C., Chen, A., Ning, J., Yi, B., Lu, K. A self-organized actomyosin drives multiple intercellular junction disruption and directly promotes neutrophil recruitment in lipopolysaccharide-induced acute lung injury.