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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 474497.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair
Authors:Marsh, L. M.; Cakarova, L.; Kwapiszewska, G.; von Wulffen, W.; Herold, S.; Seeger, W.; Lohmeyer, J.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Am J Physiol Lung Cell Mol Physiol
Issue / Number:3
Start Page:L442
End Page:52
Audience:Not Specified
Abstract / Description:Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine involved in acute lung injury and other processes such as wound repair and tumor growth. MIF exerts pro-proliferative effects on a variety of cell types including monocytes/macrophages, B cells, and gastric epithelial cell lines through binding to the major histocompatibility complex type II-associated invariant chain, CD74. In acute lung injury, inflammatory damage of the alveolar epithelium leads to loss of type I alveolar epithelial cells (AEC-I), which are replaced by proliferation and differentiation of type II alveolar epithelial cells (AEC-II). In this study we have investigated the potential of MIF to contribute to alveolar repair by stimulating alveolar epithelial cell proliferation. We show that murine AEC-II, but not AEC-I, express high surface levels of CD74 in vivo. Culture of AEC-II in vitro resulted in decreased mRNA levels for CD74 and loss of surface CD74 expression, which correlated with a transition of AEC-II to an AEC-I-like phenotype. MIF stimulation of AEC-II induced rapid and prolonged phosphorylation of ERK1/2 and Akt, increased expression of cyclins D1 and E, as well as AEC-II proliferation. Corresponding MIF signaling and enhanced thymidine incorporation was observed after MIF stimulation of MLE-12 cells transfected to overexpress CD74. In contrast, MIF did not induce MAPK activation, gene transcription, or increased proliferation in differentiated AEC-I-like cells that lack CD74. These data suggest a previously unidentified role of MIF-CD74 interaction by inducing proliferation of AEC-II, which may contribute to alveolar repair.
Free Keywords:Acute Lung Injury/genetics/immunology/pathology/physiopathology; Animals; Antigens, Differentiation, B-Lymphocyte/genetics/*metabolism; Base Sequence; Cell Differentiation; Cell Proliferation; Cells, Cultured; DNA Primers/genetics; Epithelial Cells/classification/cytology/immunology; Histocompatibility Antigens Class II/genetics/*metabolism; Macrophage Migration-Inhibitory Factors/pharmacology/*physiology; Mice; Mice, Inbred C57BL; Peptides/metabolism; Phenotype; Pulmonary Alveoli/*cytology/*immunology; Signal Transduction; Transfection
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Internal Medicine, Giessen and Marburg University, University Giessen Lung Centre, Giessen, Germany. leigh.marsh@uglc.de
Identifiers:ISSN:1040-0605 (Print) 1040-0605 (Linking)
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