Title

Differential tumor necrosis factor production by human monocyte subsets

UMMS Affiliation

Department of Surgery; Department of Medicine, Division of Gastroenterology

Date

3-1-1990

Document Type

Article

Subjects

Acetylmuramyl-Alanyl-Isoglutamine; Adult; Antigen-Presenting Cells; Antigens, Differentiation; Dinoprostone; Humans; Immune Tolerance; Interferon Type II; Middle Aged; Monocytes; Receptors, Fc; Receptors, IgG; Rosette Formation; Tumor Necrosis Factor-alpha

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: J Leukoc Biol. 1990 Mar;47(3):206-16.

Related Resources

Link to Article in PubMed

Journal Title

Journal of leukocyte biology

PubMed ID

2137848