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ToxSci Advance Access originally published online on September 2, 2009
Toxicological Sciences 2009 112(1):144-152; doi:10.1093/toxsci/kfp181
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

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

Alberto Y. Limón-Flores*,1, Rommel Chacón-Salinas*,{dagger}, Gerardo Ramos*,{ddagger},2 and Stephen E. Ullrich*,{ddagger},3

* Department of Immunology and The Center for Cancer Immunology Research, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030 {dagger} Department of Immunology, National School of Biological Sciences, ENCB-IPN, Mexico City, Mexico {ddagger} The Graduate School of Biomedical Sciences, The University of Texas, Health Sciences Center, Houston, Texas 77225

3 To whom correspondence should be addressed at the Department of Immunology-902, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Fax: (713) 563-3280. E-mail: sullrich{at}mdanderson.org.

Received August 3, 2009; accepted August 6, 2009


  Abstract

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.

Key Words: knockouts; exposure; environmental; percutaneous absorption; immunotoxicity.

1 Present address: Centro de Investigación y Assistencia en Tecnología y Diseño del Estado de Jalisco A.C., Guadalajara, Jalisco, Mexico.

2 Present address: Advanced Toxicology Research, Biosciences and Protection Division, Wright Patterson AFB, OH 45433.


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