TERMINAL DIFFERENTIATION OF MURINE RESIDENT PERITONEAL-MACROPHAGES ISCHARACTERIZED BY EXPRESSION OF THE STK PROTEIN-TYROSINE KINASE, A RECEPTOR FOR MACROPHAGE-STIMULATING PROTEIN

STK, a new member of the hepatocyte growth factor receptor family, is the receptor for macrophage-stimulating protein (MSP), which acts on m urine resident peritoneal macrophages. We established polyclonal and m onoclonal antibodies against STK and characterized the structure of ST K protein and STK expression on cells of the mononuclear phagocyte sys tem, Western blotting showed that the STK transcript is translated int o a single-chain precursor and then cleaved into a 165-kD disulfide-li nked heterodimer composed of a 35-kD alpha-chain and a 144-kD beta-cha in. Western blotting detected STK protein on resident peritoneal macro phages, a target of MSP, and showed that it was autophosphorylated in cells stimulated by MSP. By flow cytometric analysis using a monoclona l anti-STK antibody, we showed that STK protein is expressed on restri cted macrophage populations such as resident peritoneal macrophages, b ut not on exudate peritoneal macrophages or mononuclear phagocytes of the bone marrow, peripheral blood, spleen, or alveoli. Resident perito neal macrophages were classified into two fractions according to their reactivity with an anti-STK antibody and a marker antibody for macrop hages: STKhigh-F4/80(high) cells and STKnegative-F4/80(low) cells. Acu te exudative macrophages were all STKnegative-F4/80(low), but they gra dually became predominantly STKhigh-F4/80(high) several days after ent rance into the peritoneal cavity. These results showed that after mono cytes migrate into the peritoneal cavity, they undergo terminal differ entiation in the peritoneal microenvironment, This is the first eviden ce of tissue-specific terminal differentiation of peritoneal macrophag es, and this terminal differentiation can be characterized by the expr ession of STK receptor tyrosine kinase. (C) 1995 by The American Socie ty of Hematology.