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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, B. Articles by Shi, G.-P. Search for Related Content PubMed PubMed Citation Articles by Wang, B. Articles by Shi, G.-P.

Cutting Edge: Deficiency of Macrophage Migration Inhibitory Factor Impairs Murine Airway Allergic Responses¹

Bing Wang^2,*, Xiaozhu Huang^2,, Paul J. Wolters, Jiusong Sun^*, Shiro Kitamoto^*, Min Yang^*,, Richard Riese^*, Lin Leng, Harold A. Chapman, Patricia W. Finn^3,*, John R. David^¶, Richard Bucala and Guo-Ping Shi^4,*

^* Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; Department of Medicine, University of California, San Francisco, CA 94143; Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Internal Medicine, Yale University, New Haven, CT 06520; ^¶ Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA 02115

Increased levels of macrophage migration inhibitory factor (MIF) in serum, sputum, and bronchioalveolar lavage fluid (BALF) from asthmatic patients and time/dose-dependent expression of MIF in eosinophils in response to phorbol myristate acetate suggest the participation of MIF in airway inflammation. In this study, we examined inflammation in OVA-sensitized mouse lungs in wild-type and MIF-deficient mice (MIF^–/–). We report increased MIF in the lung and BALF of sensitized wild-type mice. MIF^–/– mice demonstrated significant reductions in serum IgE and alveolar inflammatory cell recruitment. Reduced Th1/Th2 cytokines and chemokines also were detected in serum or BALF from MIF^–/– mice. Importantly, alveolar macrophages and mast cells, but not dendritic cells or splenocytes, from MIF^–/– mice demonstrated impaired CD4⁺ T cell activation, and the reconstitution of wild-type mast cells in MIF^–/– mice restored the phenotype of OVA-induced airway inflammation, revealing a novel and essential role of mast cell-derived MIF in experimentally induced airway allergic diseases.

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 partially supported by a grant from the Sandler Award for Basic Science (to G.-P.S.) and National Heart, Lung, and Blood Institute Grants BI HL60942 (to G.-P.S.), HL075026 (to P.W.F.), and HL48621 (to H.A.C.), and National Institutes of Health Grant AR49610 (to R.B.).

² B.W. and X.H. contributed equally to this study.

³ Current address: Department of Medicine, University of California, San Diego, CA 92103.

⁴ Address correspondence and reprint requests to Dr. Guo-Ping Shi, Cardiovascular Medicine, NRB-7, 77th Avenue Louis Pasteur, Boston, MA 02115. E-mail address: gshi{at}rics.bwh.harvard.edu

⁵ Abbreviations used in this paper: MIF, migration inhibitory factor; BALF, bronchioalveolar lavage fluid; BMMC, bone marrow-derived mast cell; DC, dendritic cell; M, macrophage; PMN, polymorphonuclear; SMC, smooth muscle cell.