Lymphocytes produce IL-1beta in response to Fcgamma receptor cross-linking: effects on parenchymal cell IL-8 release.
Neutrophils mediate tissue injury in response to immune complexes, although the factors that induce their recruitment are incompletely understood. We have reported that lymphocytes may be important regulators of monocyte and macrophage IL-8 release in the presence of immobilized IgG. Since tissue parenchymal cells are important local producers of IL-8 but are not directly stimulated by FcgammaR cross-linking, we hypothesized that lymphocytes may also regulate parenchymal IL-8 release. Supernatants from lymphocytes incubated on immobilized IgG induced primary human fibroblasts and human mesangial cells to produce IL-8 (17 +/- 3.5 and 44 +/- 8 ng/ml, respectively). Fibroblast and mesangial cell IL-8 mRNA levels were similarly increased by the conditioned lymphocyte supernatant. Immobilized anti-human FcgammaRIII, but not FcgammaRI or FcgammaRII Abs, could stimulate this IL-8-inducing activity in lymphocytes, suggesting that FcgammaRIII-bearing lymphocytes were responsible. Supernatants from lymphocytes incubated on immobilized IgG contained 2.2 +/- 0.8 ng/ml of IL-1beta, while enriched monocyte preparations from the same donors incubated on immobilized IgG released only 0.1 +/- 0.04 ng/ml of IL-1beta (p = 0.05). Consistent with the identification of IL-1beta as the lymphocyte factor, fibroblast or mesangial cell IL-8 release induced by the IgG-stimulated lymphocyte supernatants was inhibited by 1) the combination of IL-1R antagonist and soluble type II IL-1R, 2) an IL-1-converting enzyme inhibitor, or 3) anti-IL-1beta but not preimmune Abs. These data suggest that targeted deposits of IgG can stimulate FcgammaRIII-bearing lymphocytes to produce IL-1beta, which induces parenchymal cell IL-8 release.
Marsh
C B
CB
Division of Pulmonary and Critical Care Medicine, Ohio State University, Columbus 43210, USA. marsh-3@medctr.osu.edu
Lowe
M P
MP
Rovin
B H
BH
Parker
J M
JM
Liao
Z
Z
Knoell
D L
DL
Wewers
M D
MD
D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000276:immunology; D005920:Glomerular Mesangium / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017452:Receptors, IgG / Q000737:chemistry / Q000378:metabolism*
D003432:Cross-Linking Reagents; D017077:Culture Media, Conditioned; D007074:Immunoglobulin G; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D017452:Receptors, IgG