Journal Article

Mast Cells Mediate the Immune Suppression Induced by Dermal Exposure to JP-8 Jet Fuel

Alberto Y. Limón-Flores, Rommel Chacón-Salinas, Gerardo Ramos and Stephen E. Ullrich

in Toxicological Sciences

Volume 112, issue 1, pages 144-152
Published in print November 2009 | ISSN: 1096-6080
Published online September 2009 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfp181
Mast Cells Mediate the Immune Suppression Induced by Dermal Exposure to JP-8 Jet Fuel

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Applying jet propulsion-8 (JP-8) jet fuel to the skin of mice induces immune suppression. Applying JP-8 to the skin of mice suppresses T-cell–mediated immune reactions including, contact hypersensitivity (CHS) delayed-type hypersensitivity and T-cell proliferation. Because dermal mast cells play an important immune regulatory role in vivo, we tested the hypothesis that mast cells mediate jet fuel–induced immune suppression. When we applied JP-8 to the skin of mast cell deficient mice CHS was not suppressed. Reconstituting mast cell deficient mice with wild-type bone marrow derived mast cells (mast cell “knock-in mice”) restored JP-8–induced immune suppression. When, however, mast cells from prostaglandin E2 (PGE2)–deficient mice were used, the ability of JP-8 to suppress CHS was not restored, indicating that mast cell–derived PGE2 was activating immune suppression. Examining the density of mast cells in the skin and lymph nodes of JP-8-treated mice indicated that jet fuel treatment caused an initial increase in mast cell density in the skin, followed by increased numbers of mast cells in the subcutaneous space and then in draining lymph nodes. Applying JP-8 to the skin increased mast cell expression of CXCR4, and increased the expression of CXCL12 by draining lymph node cells. Because CXCL12 is a chemoattractant for CXCR4+ mast cells, we treated JP-8-treated mice with AMD3100, a CXCR4 antagonist. AMD3100 blocked the mobilization of mast cells to the draining lymph node and inhibited JP-8–induced immune suppression. Our findings demonstrate the importance of mast cells in mediating jet fuel–induced immune suppression.

Keywords: knockouts; exposure; environmental; percutaneous absorption; immunotoxicity

Journal Article.  6257 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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