Lymphocytes produce IL-1β in response to Fcγ receptor cross-linking: Effects on parenchymal cell IL-8 release

Clay B. Marsh, Melissa P. Lowe, Brad H. Rovin, Jennifer M. Parker, Zhiming Liao, Daren L. Knoell, Mark D. Wewers

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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 FcγR 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 FcγRIII, but not FcγRI or FcγRII Abs, could stimulate this IL-8-inducing activity in lymphocytes, suggesting that FcyRIII-bearing lymphocytes were responsible. Supernatants from lymphocytes incubated on immobilized IgG contained 2.2 ± 0.8 ng/ml of IL-1β, while enriched monocyte preparations from the same donors incubated on immobilized IgG released only 0.1 ± 0.04 ng/ml of IL-1β (p = 0.05). Consistent with the identification of IL-1β 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-IR, 2) an IL-l- converting enzyme inhibitor, or 3) anti-IL-1β but not preimmune Abs. These data suggest that targeted deposits of IgG can stimulate FcγRIII-bearing lymphocytes to produce IL-1β, which induces parenchymal cell IL-8 release.

Original languageEnglish (US)
Pages (from-to)3942-3948
Number of pages7
JournalJournal of Immunology
Volume160
Issue number8
StatePublished - Apr 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Marsh, C. B., Lowe, M. P., Rovin, B. H., Parker, J. M., Liao, Z., Knoell, D. L., & Wewers, M. D. (1998). Lymphocytes produce IL-1β in response to Fcγ receptor cross-linking: Effects on parenchymal cell IL-8 release. Journal of Immunology, 160(8), 3942-3948.