Distinctive roles of neutrophil LSP1 and endothelial cell LSP1 during neutrophil recruitment (173.29)

Abstract

Abstract Leukocyte-specific protein 1 (LSP1) is an intracellular, F-actin- and Ca2+-binding, phosphoprotein expressed in leukocytes and endothelial cells (ECs). Using intravital microscopy and time-lapse video photography, we studied the role of neutrophil LSP1 (N-LSP1) and endothelial cell LSP1 (EC-LSP1) during neutrophil recruitment in the post-capillary venules in mice. The wild-type control, LSP1-deficient (Lsp1−/−) and their chimeric mice were used in this study. Neutrophil recruitment was induced by addition of chemokine MIP-2-containing gel to the observed cremasteric venule. Neutrophil intraluminal crawling, transendothelial migration, and chemotaxis in tissue were determined. We found that both N-LSP1 and EC-LSP1 were involved in neutrophil intraluminal crawling and neutrophil transendothelial migration. After neutrophil transmigration, only N-LSP1 was found to be important for neutrophil migration in the tissue, whereas EC-LSP1, but not N-LSP1, was essential for the directional neutrophil chemotaxis. Although N-LSP1 did not play an important role in neutrophil directional chemotaxis, both neutrophil migration and directional chemotaxis were dependent on the function of p38 mitogen-activated protein kinase, an upstream signaling molecule for N-LSP1, in the emigrated neutrophils in the tissue. Our results suggest that N-LSP1 and EC-LSP1 are both important for neutrophil recruitment but play distinctive roles in different steps of neutrophil recruitment in vivo.