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Originally published online as doi:10.2353/ajpath.2008.070559 on May 8, 2008

Published online before print May 8, 2008
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(American Journal of Pathology. 2008;172:1638-1649.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070559

Mast Cells Regulate the Magnitude and the Cytokine Microenvironment of the Contact Hypersensitivity Response

M. Ursula Norman*, John Hwang*, Sara Hulliger*, Claudine S. Bonder{dagger}, Jun Yamanouchi{ddagger}, Pere Santamaria{ddagger} and Paul Kubes{dagger}

From the Immunology Research Group,* the Department of Physiology and Biophysics,{dagger} the Julia McFarlane Diabetes Research Centre, and the Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Canada; and the Hanson Institute,{ddagger} Institute of Medical and Veterinary Science, Adelaide, Australia

The role that mast cells play during contact hypersensitivity (CS) response is unclear because some studies have shown that mast cell-deficient mice have relatively intact CS responses whereas others have shown opposing results. Mast cells secrete a wide range of immunomodulatory mediators and can potentially influence the type of immune response generated in the skin during CS. Therefore, we examined the type of microenvironment generated during CS in both W/Wv mast cell-deficient and wild-type mice in response to different immunizing doses of hapten (oxazolone). The CS response elicited after low-dose oxazolone was significantly diminished in W/Wv mice compared with wild-type mice. Unexpectedly, the CS response elicited in W/Wv mice immunized with high-dose oxazolone was more severe compared with wild-type mice. In addition, after immunization with high-dose oxazolone, the granulocyte infiltrate in W/Wv mice was increased by twofold compared with wild-type mice. A shift in the cytokine milieu toward the expression of type-1 cytokines as well as a significant increase in the local adhesion of neutrophils and CD4 T cells in the microvasculature of the skin was observed after hapten challenge in W/Wv mice immunized with high-dose oxazolone compared with wild-type mice. These results suggest that mast cells can act as regulators and inducers of the inflammatory response depending on immunizing stimulus strength.




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