TERMINAL DIFFERENTIATION OF MURINE RESIDENT PERITONEAL-MACROPHAGES IS CHARACTERIZED BY EXPRESSION OF THE STK PROTEIN-TYROSINE KINASE, A RECEPTOR FOR MACROPHAGE-STIMULATING PROTEIN
TERMINAL DIFFERENTIATION OF MURINE RESIDENT PERITONEAL-MACROPHAGES IS CHARACTERIZED BY EXPRESSION OF THE STK PROTEIN-TYROSINE KINASE, A RECEPTOR FOR MACROPHAGE-STIMULATING PROTEIN
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DOI：
10.1182/blood.v86.9.3394.bloodjournal8693394
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发表时间：
1995-11-01
期刊：
影响因子：
20.3
通讯作者：
SUDA, T
中科院分区：
文献类型：
--
作者：
IWAMA, A;WANG, MH;SUDA, T
STK是肝细胞生长因子受体家族的新成员，是巨噬细胞刺激蛋白(MSP)的受体，作用于小鼠常驻的腹膜巨噬细胞。我们建立了抗STK的多克隆和单克隆抗体，并鉴定了STK蛋白的结构和STK在单核吞噬细胞系统中的表达。Western blotting表明，STK转录本被翻译成单链前体，然后被切割成由35kD的α链和144kD的β链组成的165kD的二硫键连接的异源二聚体。Western blotting检测到MSP靶点驻留的腹膜巨噬细胞上的STK蛋白，并表明在MSP刺激的细胞中STK蛋白被自动磷酸化。通过使用抗STK单抗的流式细胞仪分析，我们发现STK蛋白表达在限制性巨噬细胞群上，例如常驻的腹膜巨噬细胞，但不表达在渗出的腹膜巨噬细胞或骨髓、外周血、脾或肺泡的单核巨噬细胞上。根据其与抗STK抗体和巨噬细胞标志性抗体的反应性，将常驻的腹膜巨噬细胞分为两组：STKHigh-F4/80(高)细胞和STK-F4/80(低)细胞。急性渗出性巨噬细胞均为STK阴性-F4/80(低)，但进入腹膜后几天逐渐以STK高-F4/80(高)为主。这些结果表明，单核细胞迁移到腹膜腔后，在腹膜微环境中经历了终末分化，这是腹膜巨噬细胞组织特异性终末分化的第一个证据，这种终末分化可以通过STK受体酪氨酸激酶的表达来表征。(C)1995年由美国血液病学会主办。
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-F4/80(high) cells and STKnegative-F4/80(low) cells. Acute exudative macrophages were all STKnegative-F4/80(low), but they gradually became predominantly STKhigh-F4/80(high) 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. (C) 1995 by The American Society of Hematology.