Proteolytic cleavage and activation of pro-macrophage-stimulating protein by resident peritoneal macrophage membrane proteases.
نویسندگان
چکیده
Macrophage stimulating protein (MSP), which is secreted as biologically inactive pro-MSP, is activated to MSP by cleavage at a single peptide bond. Our objectives were to determine the form of MSP in circulating blood and to study proteolytic activation of pro-MSP by its target cell. Western blot of immunoaffinity-purified serum MSP showed that all the protein was pro-MSP, without detectable MSP. The circulating form of the protein is therefore pro-MSP, and conversion to MSP does not occur when blood is shed. Incubation of radiolabeled pro-MSP with murine peritoneal macrophages caused proteolytic cleavage to predominantly inactive fragments. Among several protease inhibitors, soybean trypsin inhibitor was one of two that inhibited nonspecific cleavage and revealed a macrophage proteolysis of pro-MSP, and certain concentrations enhanced cleavage to mature MSP. Macrophage membranes had nonspecific and specific pro-MSP proteolytic activity, which was not present in macrophage culture fluids. The results suggest that control of MSP activity can occur at the level of the target cell by proteolytic cleavage of pro-MSP to mature MSP or to inactive fragments.
منابع مشابه
Impairment of Macrophage Presenting Ability and Viability by Echinococcus granulosus Antigens
Background: Despite advances toward an improved understanding of the evasive mechanisms leading to the establishment of cystic echinococcosis, the discovery of specific immunosuppressive mechanisms and related factors are of great interest in the development of an immunotherapeutic approach. Objective: To elucidate immunosuppressive effects of bioactive factors contained in chromatographic frac...
متن کاملAngiogenesis, Metastasis, and the Cellular Microenvironment Proteolytic Activation of Pro-Macrophage-Stimulating Protein by Hepsin
Macrophage-stimulating protein (MSP) is a plasminogen-related growth factor and ligand for the receptor tyrosine kinase RON. TheMSP/RON system promotes wound healing and invasive tumor growth and suppresses proinflammatory immune response. MSP binding to RON requires proteolytic conversion of the inactive singlechain form (pro-MSP) into the disulfide-linked a/b heterodimer. The pro-MSP cleavage...
متن کاملProteolytic activation of pro-macrophage-stimulating protein by hepsin.
Macrophage-stimulating protein (MSP) is a plasminogen-related growth factor and ligand for the receptor tyrosine kinase RON. The MSP/RON system promotes wound healing and invasive tumor growth and suppresses proinflammatory immune response. MSP binding to RON requires proteolytic conversion of the inactive single-chain form (pro-MSP) into the disulfide-linked α/β heterodimer. The pro-MSP cleava...
متن کاملP-153: Role of Chemokines in The Pathogenesis of Infertility Related to Enometriosis
Background: Chemokines, proteins that operate within the body's immune system, play numerous roles in menstruation, bacterial infection, implantation of embryos, and the maintenance of early pregnancy. They are also strongly related to the pathogenesis of endometriosis. Materials and Methods: This is review article that were indentifical by computer search of MEDLINE (1984- 2013). Results:...
متن کاملExpression of a Chimeric Protein Containing the Catalytic Domain of Shiga-Like Toxin and Human Granulocyte Macrophage Colony-Stimulating Factor (hGM-CSF) in Escherichia coli and Its Recognition by Reciprocal Antibodies
Fusion of two genes at DNA level produces a single protein, known as a chimeric protein. Immunotoxins are chimeric proteins composed of specific cell targeting and cell killing moieties. Bacterial or plant toxins are commonly used as the killing moieties of the chimeric immunotoxins. In this investigation, the catalytic domain of Shiga-like toxin (A1) was fused to human granulocyte macrophage ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of clinical investigation
دوره 97 3 شماره
صفحات -
تاریخ انتشار 1996