Differential Tumor Necrosis Factor Production by Human Monocyte Subsets

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Abstract
The human monocyte (MØ) 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 MØ subset (FcRI-) is the major plasminogen activator-producing and antigen-presenting MØ. This study gives additional evidence for the functional disparity of the FcRI- and FcRI+ MØ subsets. We are demonstrating that the normal human MØ subset isolated by rosetting via the FcRI receptor (FcRI+) produces greater quantities of tumor necrosis factor (TNF) than the non-rosetting (FcRI-) MØ. TNF production by the FcRI+ MØ subset is greater than that of the FcRI- MØ subset whether secreted (P < .001) or cell-associated (P < .001) TNF is assessed. The rosetting MØ subset that expresses high densities of FcRI (FcRI+) produced the majority of normal human peripheral blood MØ TNF whether the stimulation was an interferon gamma (IFNγ) prime followed by MDP or followed by interleukin-2 (IL-2). The Fc rosetting technique itself resulted in some TNF induction in the FcRI+ MØ subset accounting for some of the increased TNF production of this subset. However, increasing the stimulation level of the FcRI very-low-density (FcRI-) MØ subset did not induce it to produce TNF levels equivalent to the moderately stimulated FcRI+ MØ subset. These data, therefore, imply that only stimulation through the type I Fcγ receptor can augment or induce TNF activity. The difference in the MØ subset's TNF response remained even after the FcRI- MØ subset received a 2.5-fold increase in stimulation with the classical MØ induction regimen of IFNγ plus bacterial cell wall product. Although stimulation of the FcRI+ MØ 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-) MØ subset, again indicating functional disparity between these subsets. Greater TNF production by the FcRI+ MØ 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- MØ ratio in these patients coupled to the functional differences in FcRI+ and FcRI+ MØ subsets could be one mechanism for the development of immunoincompetence.