LSP1 modulates leukocyte populations in resting and inflamed peritoneum

Lymphocyte-specific protein 1, recently renamed leukocyte-specific protein 1 (LSP1), is an F-actin binding protein expressed in lymphocytes, macrophag es, and neutrophils in mice and humans, This study examines LSP1-deficient (Lsp1(-/-)) mice for the development of myeloid and lymphocytic cell popula tions and their response to the development of peritonitis induced by thiog lycollate (TG) and to a T-dependent antigen. Lsp1(-/-) mice exhibit signifi cantly higher levels of resident macrophages in the peritoneum compared to wild-type (wt) mice, whereas the development of myeloid cells is normal. Th is increase, which is specific for conventional CD5(-) macrophages appears to be tissue specific and does not result from differences in adhesion to t he peritoneal mesothelium, The level of peritoneal lymphocytes is decreased in Lsp1(-/-) mice without affecting a particular lymphocytic subset. The p roportions of precursor and mature lymphocytes in the central and periphera l tissues of Lsp1(-/-) mice are similar to those of wt mice and Lsp1(-/-) m ice mount a normal response to the T-dependent antigen, ovalbumin (OVA), On injection of TG, the Lsp1(-/-) mice exhibit an accelerated kinetics of cha nges in peritoneal macrophage and neutrophil numbers as compared to wt incl uding increased influx of these cells. LSP1(-) neutrophils demonstrate an e nhanced chemotactic response in vitro to N-formyl methionyl-leucyl-phenylal anine (FMLP) and to the C-X-C chemokine, KC, indicating that their enhanced influx into the peritoneum may be a result of increased motility, Our data demonstrate that LSP1 is a negative regulator of neutrophil chemotaxis. (C ) 2000 by The American Society of Hematology.