title: Differential tumor necrosis factor production by human monocyte subsets.
abstract: The human monocyte (M phi subset rosetting with anti RH-coated human erythrocytes via high-affinity, 72 kD receptors (FcRI+), contains the PGE2-producing immunosuppressive subpopulation, while the non-rosetting M phi subset (FcRI-) is the major plasminogen activator-producing and antigen-presenting M phi. This study gives additional evidence for the functional disparity of the FcRI- and FcRI+ M phi subsets. We are demonstrating that the normal human M phi subset isolated by rosetting via the FcRI receptor (FcRI+) produces greater quantities of tumor necrosis factor (TNF) than the non-rosetting (FcRI-) M phi. TNF production by the FcRI+ M phi subset is greater than that of the FcRI- M phi subset whether secreted (P less than .001) or cell-associated (P less than .001) TNF is assessed. The rosetting M phi subset that expresses high densities of FcRI (FcRI+) produced the majority of normal human peripheral blood M phi TNF whether the stimulation was an interferon gamma (IFN gamma) prime followed by MDP or followed by interleukin-2 (IL-2). The Fc rosetting technique itself resulted in some TNF induction in the FcRI+ M phi subset accounting for some of the increased TNF production of this subset. However, increasing the stimulation level of the FcRI very-low-density (FcRI-) M phi subset did not induce it to produce TNF levels equivalent to the moderately stimulated FcRI+ M phi subset. These data, therefore, imply that only stimulation through the type I Fc gamma receptor can augment or induce TNF activity. The difference in the M phi subset's TNF response remained even after the FcRI- M phi subset received a 2.5-fold increase in stimulation with the classical M phi induction regimen of IFN gamma plus bacterial cell wall product. Although stimulation of the FcRI+ M phi subset via crosslinking of their FcRI receptors might represent a unique TNF stimulation pathway, this stimulation does not occur in the low-density FcRI (FcRI-) M phi subset, again indicating functional disparity between these subsets. Greater TNF production by the FcRI+ M phi subset was induced concomitant to elevation of its prostaglandin E2 production. Since both TNF and PGE2 are increased in some patient groups, a pathological shift in the FcRI+ versus FcRI- M phi ratio in these patients coupled to the functional differences in FcRI+ and FcRI- M phi subsets could be one mechanism for the development of immunoincompetence.
authors: Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
authors: G
authors: G
authors: Szabo
authors: C L
authors: CL
authors: Miller-Graziano
authors: J Y
authors: JY
authors: Wu
authors: T
authors: T
authors: Takayama
authors: K
authors: K
authors: Kodys
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000328:Adult; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000943:Antigens, Differentiation / Q000032:analysis*; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000032:analysis*; D017452:Receptors, IgG; D012397:Rosette Formation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000943:Antigens, Differentiation; D011961:Receptors, Fc; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; D015232:Dinoprostone