HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Abel, M. Articles by Vliagoftis, H. PubMed PubMed Citation Articles by Abel, M. Articles by Vliagoftis, H.

Mast Cell-Fibroblast Interactions Induce Matrix Metalloproteinase-9 Release from Fibroblasts: Role for IgE-Mediated Mast Cell Activation¹

Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

Mast cells adhere to fibroblasts, but the biological effects of adhesion are not well understood. We hypothesized that these adhesive interactions are important for tissue remodeling through the release of matrix metalloproteinases (MMP). Murine bone marrow cultured mast cells (BMCMC) were cocultured with NIH-3T3 fibroblasts or murine lung fibroblasts (CCL-206) and supernatants analyzed for MMP-9 release by gelatin zymography. Coculture of BMCMC for 24 h with NIH-3T3 or CCL-206 fibroblasts increased the release of MMP-9 from fibroblasts by 1.7 ± 0.2 and 2.0 ± 0.7-fold, respectively. Coculture of BMCMC and fibroblasts in the presence of IgE increased further MMP-9 release, which was released by fibroblasts. MMP-9 release was dependent on TNF released from IgE activated BMCMC and on adhesive interactions between BMCMC and fibroblasts. Increased MMP-9 release was also p44/42-dependent, as was MMP-9 up-regulation during coculture of fibroblasts with resting BMCMC. Finally, IgE injection into the mouse ear increased MMP-9 content of the ear tissue in the absence of Ag, indicating that IgE-mediated remodeling may play a pathogenic role in allergic conditions even in the absence of exposure to allergens. In conclusion, mast cell-fibroblast interactions induce the release of proteases important for tissue remodeling, such as MMP-9. MMP-9 release was further increased in the presence of IgE during coculture, suggesting a role for mast cell-fibroblast interactions in atopic conditions.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Canadian Institutes of Health Research, Alberta Heritage Foundation for Medical Research, and The Lung Association of Alberta and Northwest Territories. H.V. is an Alberta Heritage Foundation for Medical Research Scholar.

² Address correspondence and reprint requests to Dr. Harissios Vliagoftis, Pulmonary Research Group, Department of Medicine, 550 Heritage Medical Research Center, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada. E-mail address: harissios.vliagoftis{at}ualberta.ca

³ Abbreviations used in this paper: ECM, extracellular matrix; MMP, matrix metalloproteinase; FN, fibronectin; HA, hemagglutinin; BMCMC, bone marrow cultured mast cell; TIMP, tissue inhibitor of metalloproteinase.