Endothelial-expressed leukocyte-specific protein 1 regulates intravascular and extravascular directionality of chemotaxing neutrophils (P5094)

Abstract

Abstract The endothelial-expressed Ca2+- and F-actin-binding leukocyte-specific protein 1 (LSP1) was shown to play a pivotal role in the regulation of endothelial transmigratory cup formation, microvascular permeability increases, and transendothelial migration of leukocytes. Due to the complexity of leukocyte-endothelial interactions, the cell-specific role of LSP1 is incompletely understood. To elucidate the orchestration of neutrophil dynamics by endothelial LSP1 in vivo, intravital microscopy and time-lapsed video analysis were performed in the microvasculature of cremaster muscle in LSP1-deficient chimeric mice. Absence of LSP1 (Lsp1−/−) in non-hematopoietic tissue resulted in significantly impaired chemotactic directionality (chemotaxis index) but not the neutrophil migration velocity during CXCL2-elicited intraluminal crawling and extravascular migration as compared to the responses in wild type (Lsp1+/+) endothelial cells. The velocity of migration of Lsp1−/− neutrophils in extravascular tissue was significantly lower in both Lsp1+/+ and Lsp1−/− chimeric mice as compared to that of Lsp1+/+ neutrophils in these mice. Analysis of integrin expression of transmigrated neutrophils from CXCL2-induced peritonitis in chimeric mice revealed blunted expression of α6 and β1 on neutrophils only in mice with Lsp1−/− endothelial cells. In conclusion, non-hematopoietic endothelial LSP1 is a novel regulator of neutrophil directionality during neutrophil recrutment.