title: Production, characterization, and interspecies reactivities of monoclonal antibodies against human class A macrophage scavenger receptors.
abstract: Class A macrophage scavenger receptor (SR-A) is one of the major receptors of macrophages and plays important roles in atherogenesis and host defense mechanisms. To assess the role of SR-A, monoclonal antibodies were generated by immunizing SR-A-deficient mice with a recombinant protein of human type I SR-A as immunogen. Four antibodies (SRA-C6, SRA-D10, SRA-E5, and SRA-F8) were confirmed to be specific for SR-A by Western blot analysis. In early atherosclerotic lesions, these antibodies recognized scattered macrophages in intima and foamy macrophages in the periphery of atheromatous cores. Interestingly, foamy macrophages in the core lesion were only weakly stained. In other organs, the antibodies recognized tissue macrophages such as alveolar macrophages, Kupffer cells in the liver, red pulp macrophages in the spleen, sinus macrophages in lymph nodes, and interstitial macrophages in various organs. Perivascular macrophages in the brain (Mato cells) were also positive for these antibodies. Freshly isolated blood monocytes were negative; however, they became positive for these antibodies after 1 day in culture. At 3-5 days in culture, the reaction intensity became stronger along their differentiation towards macrophages. Dendritic cells such as interdigitating cells of lymphoid tissues and epidermal Langerhans cells were invariably negative. In the reaction with animal tissues, each antibody showed a unique reaction pattern. Among four antibodies, SRA-E5 recognized SR-A molecules in all animal species examined, including rats and mice. These antibodies will be useful tools for the study of SR-A in atherogenesis and various other pathological conditions in humans and animal species.
authors.affiliation: Second Department of Pathology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Ryu ichiro
authors.initials: Ri
authors.lastname: Tomokiyo
authors.forename: Katsunori
authors.initials: K
authors.lastname: Jinnouchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Honda
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Norihisa
authors.initials: N
authors.lastname: Hanada
authors.forename: Takehisa
authors.initials: T
authors.lastname: Hiraoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D000918:Antibody Specificity; D015153:Blotting, Western; D002417:Cattle; D002460:Cell Line; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011971:Receptors, Immunologic / Q000276:immunology*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D013045:Species Specificity
chemical_list: D000911:Antibodies, Monoclonal; C495139:MSR1 protein, human; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A