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Blood, 1 September 2000, Vol. 96, No. 5, pp. 1827-1835
IMMUNOBIOLOGY
LSP1 modulates leukocyte populations in resting and
inflamed peritoneum
Jenny Jongstra-Bilen,
Virginia L. Misener,
Chunjie Wang,
Hedy Ginzberg,
Anna Auerbach,
Alexandra L. Joyner,
Gregory P. Downey, and
Jan Jongstra
From the Toronto Western Research Institute, Cell and
Molecular Biology Division and Department of Immunology, Division of
Respirology, Department of Medicine, University of Toronto, and Toronto
General Division of the University Health Network, Toronto,
Canada; New York University Medical Center, Skirball Institute of
Biomolecular Medicine, Developmental Genetics Program, New York, NY.
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.
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