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, macrophages, and neutrophils in mice and humans. This study examines LSP1-deficient (Lsp1(-/-)) mice for the development of myeloid and lymphocytic cell populations and their response to the development of peritonitis induced by thioglycollate (TG) and to a T-dependent antigen. Lsp1(-/-) mice exhibit significantly higher levels of resident macrophages in the peritoneum compared to wild-type (wt) mice, whereas the development of myeloid cells is normal. This increase, which is specific for conventional CD5(-) macrophages appears to be tissue specific and does not result from differences in adhesion to the peritoneal mesothelium. The level of peritoneal lymphocytes is decreased in Lsp1(-/-) mice without affecting a particular lymphocytic subset. The proportions of precursor and mature lymphocytes in the central and peripheral tissues of Lsp1(-/-) mice are similar to those of wt mice and Lsp1(-/-) mice mount a normal response to the T-dependent antigen, ovalbumin (OVA). On injection of TG, the Lsp1(-/-) mice exhibit an accelerated kinetics of changes in peritoneal macrophage and neutrophil numbers as compared to wt including increased influx of these cells. LSP1(-) neutrophils demonstrate an enhanced chemotactic response in vitro to N-formyl methionyl-leucyl-phenylalanine (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. (Blood. 2000;96:1827-1835)
Jongstra-Bilen
J
J
Toronto Western Research Institute, Cell and Molecular Biology Division and Department of Immunology, University of Toronto, Ontario, Canada. jblien@uhnres.utoronto.ca
Misener
V L
VL
Wang
C
C
Ginzberg
H
H
Auerbach
A
A
Joyner
A L
AL
Downey
G P
GP
Jongstra
J
J
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D018956:CD5 Antigens / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D007700:Kinetics; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010537:Peritoneum / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D013864:Thioglycolates / Q000008:administration & dosage / Q000009:adverse effects
D018956:CD5 Antigens; D002135:Calcium-Binding Proteins; C057701:Lsp1 protein, mouse; D008840:Microfilament Proteins; D013864:Thioglycolates; D010047:Ovalbumin