Identification of the integral membrane protein RM3/1 on human monocytes as a glucocorticoid-inducible member of the scavenger receptor cysteine-rich family (CD163).
The RM3/1 Ag is a membrane glycoprotein restricted to human monocytes and macrophages that evolve in the late phase of inflammation. Peptide sequence analysis of the RM3/1 protein revealed similarity to CD163, a member of the scavenger receptor cysteine-rich family. Using specific Abs (RM3/1, Ki-M8), we demonstrate an identical cellular regulation for the RM3/1 and the CD163 protein. Most notably, we show for the first time that CD163 is significantly up-regulated by glucocorticoids. In contrast, the protein is down-regulated by the immunosuppressant cyclosporin A and by phorbol esters, while the inflammatory mediator LPS has no significant influence on the expression. We describe the first isolation of a full-length cDNA of CD163 and expression of the corresponding protein. Several splice variants of CD163 exist, and we elucidated the kinetics of induction of three major mRNA splice variants by fluticasone propionate; another splice variant was proved to be unresponsive to this glucocorticoid. Taken together with a previous result showing an involvement of RM3/1 in adhesion of monocytes to the activated endothelium, we discuss that CD163 might play an important role in inflammatory processes.
Institute of Experimental Dermatology, Westfälische Wilhelms-University Münster, Germany. hogger@uni-muenster.de
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D000287:Administration, Topical; D017398:Alternative Splicing / Q000276:immunology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D015153:Blotting, Western; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary / Q000302:isolation & purification; D005434:Flow Cytometry; D000068298:Fluticasone; D005786:Gene Expression Regulation / Q000276:immunology; D015723:Gene Library; D005938:Glucocorticoids; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000097:blood / Q000737:chemistry*; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D017421:Sequence Analysis; D000098902:CD163 Antigen
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D018076:DNA, Complementary; D005938:Glucocorticoids; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D000068298:Fluticasone