Cutting edge: Deficiency of macrophage migration inhibitory factor impairs murine airway allergic responses.
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.
Wang
Bing
B
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77th Avenue Louis Pasteur, Boston, MA 02115, USA.
Huang
Xiaozhu
X
Wolters
Paul J
PJ
Sun
Jiusong
J
Kitamoto
Shiro
S
Yang
Min
M
Riese
Richard
R
Leng
Lin
L
Chapman
Harold A
HA
Finn
Patricia W
PW
David
John R
JR
Bucala
Richard
R
Shi
Guo-Ping
GP
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D016676:Macrophages, Alveolar / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D007073:Immunoglobulin E; D010047:Ovalbumin