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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.

Biedermann T, Kneilling M, Mailhammer R, Maier K, Sander CA, Kollias G, Kunkel SL, Hültner L, Röcken M - J. Exp. Med. (2000)

Bottom Line: 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.Thus, mast cell-derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell-mediated DTHRs.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, 80337 Munich, Germany.

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.

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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.

Biedermann T, Kneilling M, Mailhammer R, Maier K, Sander CA, Kollias G, Kunkel SL, Hültner L, Röcken M - J. Exp. Med. (2000)

© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2193186&req=5

Bottom Line: 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.Thus, mast cell-derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell-mediated DTHRs.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, 80337 Munich, Germany.

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.

Show MeSH
Related in: MedlinePlus