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Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2
Author(s): Biedermann T, Kneilling M, Mailhammer R, Maier K, Sander CA, Kollias G, Kunkel SL, Hultner L, Rocken M
Source: JOURNAL OF EXPERIMENTAL MEDICINE    Volume: 192    Issue: 10    Pages: 1441-1451    Published: NOV 20 2000  
Times Cited: 168     References: 63     
Abstract: Polymorphonuclear leukocytes (PMNs) characterize the pathology of T cell-mediated autoimmune diseases and delayed-type hypersensitivity reactions (DTHRs) in the skin, joints, and gut, but are absent in T cell-mediated autoimmune diseases of the brain or pancreas. All of these reactions are mediated by interferon gamma -producing type 1 T cells and produce a similar pattern of cytokines. Thus, the cells and mediators responsible for the PMN recruitment into skin, joints, or gut during DTHRs remain unknown. Analyzing hapten-induced DTHRs of the skin, we found that mast cells determine the T cell-dependent PMN recruitment through two mediators, tumor necrosis factor (TNF) and the CXC chemokine macrophage inflammatory protein 2 (MIP-2), the functional analogue of human interleukin 8. Extractable MIP-2 protein was abundant during DTHRs in and around mast cells of wild-type (WT) mice but absent in mast cell-deficient WBB6F(1)-Kit(W)/Kit(W-v) (Kit(W)/Kit(W-v)) mice. T cell-dependent PMN recruitment was reduced >60% by anti-MIP-2 antibodies and >80% in mast cell-deficient Kit(W)/Kit(W-v) mice. Mast cells from WT mice efficiently restored DTHRs and MIP-2-dependent PMN recruitment in Kit(W)/Kit(W-v) mice. whereas mast cells from TNF-/- mice did not. Thus, mast cell-derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell-mediated DTHRs.
Document Type: Article
Language: English
Reprint Address: Rocken, M (reprint author), Univ Munich, Dept Dermatol & Allergol, Frauenlobstr 9-11, D-80337 Munich, Germany
Addresses:
1. Univ Munich, Dept Dermatol & Allergol, D-80337 Munich, Germany
2. Inst Clin Mol Biol & Tumor Genet, D-81377 Munich, Germany
3. GSF, Natl Res Ctr Environm & Hlth, Inst Inhalat Biol, D-80807 Munich, Germany
4. Hellen Pasteur Inst, Athens 11521, Greece
5. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
Subject Category: Immunology; Medicine, Research & Experimental
IDS Number: 375ZH
ISSN: 0022-1007
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