Selective induction of Fc gamma RIII on human monocytes by transforming growth factor-beta.
Transforming growth factor-beta (TGF-beta) is a polypeptide that participates in morphogenesis, inflammation, and would repair. Emerging as an important immunomodulatory molecule, TGF-beta may also regulate the phenotype and function of mononuclear cells within an inflammatory site. In this study TGF-beta is shown to induce expression of the gp50-65 receptor for Fc gamma RIII on otherwise negative peripheral blood monocytes. Circulating monocytes express Fc gamma RI and Fc gamma RII, but not Fc gamma RIII, and no inducing agent for Fc gamma RIII has previously been identified. Within hours after exposure of freshly isolated peripheral blood monocytes to picomolar concentrations of TGF-beta 1 or TGF-beta 2, mRNA specific for Fc gamma RIII is detectable followed by expression of the receptors on the cell surface. Neutralizing antibodies to TGF-beta completely inhibit the TGF-beta-induced up-regulation of Fc gamma RIII. In contrast to TGF-beta, other cytokines involved in the inflammatory response are ineffective in regulating Fc gamma RIII expression on human monocytes. Thus, the early release of TGF-beta by platelets in an inflammatory site may foster enhanced immunophagocytosis and contribute to host defense by inducing monocyte Fc gamma RIII expression.
Welch
G R
GR
Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Wong
H L
HL
Wahl
S M
SM
D000943:Antigens, Differentiation / Q000096:biosynthesis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001685:Biological Factors / Q000494:pharmacology; D015152:Blotting, Northern; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011961:Receptors, Fc / Q000096:biosynthesis*; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015291:Transforming Growth Factors / Q000494:pharmacology*
D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D001685:Biological Factors; D016207:Cytokines; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2; D015291:Transforming Growth Factors