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Fox BA, Petty HR: Characterization of a monoclonal antibody defining a macrophage activation-specific cell surface antigen. Mol Immunol. 1984 Jul;21(7):681-4.
Macrophages have been obtained from the peritoneal cavities of C57BL/6 mice following treatment with C. parvum, MVE-2, mineral oil, or thioglycollate. Cell populations were primarily composed of mononuclear phagocytes as determined by a latex bead uptake assay. Macrophages obtained from C. parvum or MVE-2 were activated as judged by enhanced cytostatic activity against two tumor cell target lines. Thioglycollate-elicited macrophages demonstrated much lower cytostatic ability. Rats were immunized with activated MVE-2 macrophages. Hybridomas were prepared by fusion with a non-secreting myeloma cell line followed by cloning. Cell supernates were selected on the basis of binding to activated but not elicited macrophages. The monoclonal antibody produced has been characterized by flow cytometry. The antibody does not react with syngeneic erythrocytes, thymocytes, or spleen cells. Reaction with thioglycollate macrophages is very low. Alternatively, intense binding is found on activated macrophages. This antigen which accompanies macrophage activation for tumor cell cytostasis is designated as macrophage activation antigen-1 (MAA-1). Several important physiological changes accompany the process of macrophage activation. For example, activated macrophages demonstrate enhanced microbicidal, phagocytic, secretory, and tumoricidal activity (for reviews see refs. 1,2). Concommitant alterations in cell surface properties have been observed. These include: (a) changes in surface morphology and spreading (3-5), (b) altered lipid and protein content (6,7), (c) decreases in 5'-nucleotidase activity and alkaline phosphodiesterase (8), increases in leucine aminopeptidase (8), decreases in mannose receptors (11,12), and antigen F4/80 (11), (d) increases in Ia antigens (11,12), and (e) increased tumor cell binding (13). These structural and functional modifications indicate that activated macrophages represent a unique class of functionally differentiated cells (9). Antigenic modifications accompanying macrophage differentiation are of special interest. Markers for specific macrophage classes might be useful in defining differentiation pathways, dissecting type-specific functional activities such as tumor cytotoxicity, and providing a means to identify macrophage subsets in heterogeneous cell populations. In the present work we have taken the first step in this direction by defining a cell surface macrophage activation antigen. |
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