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Terminal differentiation of murine resident peritoneal macrophages is
characterized by expression of the STK protein tyrosine kinase, a receptor
for macrophage-stimulating protein
A Iwama, MH Wang, N Yamaguchi, N Ohno, K Okano, T Sudo, M Takeya, F Gervais, C Morissette and EJ Leonard
Department of Cell Differentiation, Kumamoto University School of Medicine,
Japan.
STK, a new member of the hepatocyte growth factor receptor family, is the
receptor for macrophage-stimulating protein (MSP), which acts on murine
resident peritoneal macrophages. We established polyclonal and monoclonal
antibodies against STK and characterized the structure of STK protein and
STK expression on cells of the mononuclear phagocyte system. Western
blotting showed that the STK transcript is translated into a single-chain
precursor and then cleaved into a 165-kD disulfide- linked heterodimer
composed of a 35-kD alpha-chain and a 144-kD beta- chain. Western blotting
detected STK protein on resident peritoneal macrophages, a target of MSP,
and showed that it was autophosphorylated in cells stimulated by MSP. By
flow cytometric analysis using a monoclonal anti-STK antibody, we showed
that STK protein is expressed on restricted macrophage populations such as
resident peritoneal macrophages, but not on exudate peritoneal macrophages
or mononuclear phagocytes of the bone marrow, peripheral blood, spleen, or
alveoli. Resident peritoneal macrophages were classified into two fractions
according to their reactivity with an anti-STK antibody and a marker
antibody for macrophages: STKhigh-F4/80high cells and STKnegative- F4/80low
cells. Acute exudative macrophages were all STKnegative- F4/80low, but they
gradually became predominantly STKhigh-F4/80high several days after
entrance into the peritoneal cavity. These results showed that after
monocytes migrate into the peritoneal cavity, they undergo terminal
differentiation in the peritoneal microenvironment. This is the first
evidence of tissue-specific terminal differentiation of peritoneal
macrophages, and this terminal differentiation can be characterized by the
expression of STK receptor tyrosine kinase.
Volume 86,
Issue 9,
pp. 3394-3403,
11/01/1995
Copyright © 1995 by The American Society of Hematology
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