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.

Failure of Monocytes of Trauma Patients to Convert to Immature Dendritic Cells is Related to Preferential Macrophage-Colony-Stimulating Factor-Driven Macrophage Differentiation

“…Increased circulating CD64 ϩ inflammatory Macs have been previously described in injury, and these more inflammatory Mac have altered function (41, 44 -46). We have previously reported that trauma patient M with high CD64 expression produce exaggerated amounts of the 26-kDa, cell-associated form of TNF-␣ with increased TNF-␣ mRNA stability (1,47). A recent report describes hM-CSF-differentiated PBMC Mac as producing higher TNF levels than M because of their increased TNF mRNA stability.…”

Neutrophil secretion products pave the way for inflammatory monocytes

“…38 Classical human monocytes are potent phagocytes 39 and produce higher amounts of cytokines like IL-6 and TNF. 40,41 In contrast, nonclassical monocytes are potent antigen-presenting cells. 42 Such distinct differences have not yet been described for the murine equivalent.…”

Neutrophil-derived azurocidin alarms the immune system

“…This population of murine monocytes shares morphological characteristics and chemokine receptor expression patterns with the classical human CD14 hi CD16 -monocytes, and murine resident monocytes are thought to correspond to human CD14 ϩ CD16 ϩ nonclassical monocytes [34]. Human classical monocytes are potent phagocytes [37] and produce higher amounts of cytokines such as IL-6 and TNF-␣ [38,39]. In contrast, nonclassical monocytes are potent APC [40].…”