Copyright © 2007 American Academy of Allergy, Asthma & Immunology Published by Mosby, Inc.
Human mast cells release oncostatin M on contact with activated T cells: Possible biologic relevance
aFrom the Allergy and Clinical Immunology Laboratory
bDepartment of Pharmacology, Faculty of Medicine, the Hebrew University, Jerusalem
cMicrobiology Laboratory, Meir General Hospital, Kfar Saba, and the Sackler School of Medicine, Tel Aviv University
Received 7 December 2006; revised 22 August 2007; accepted 30 August 2007. Kfar Saba, Tel Aviv, and Jerusalem, Israel. Available online 29 October 2007.
We have recently demonstrated that mast cells can be activated by heterotypic adhesion to activated T cells.
We sought to perform gene expression profiling on human mast cells activated by either IgE cross-linking or by T cells and to characterize one of the cytokines, oncostatin M (OSM).
Gene expression profiling was done by means of microarray analysis, OSM expression was validated by means of RT-PCR, and the product was measured by means of ELISA in both the LAD 2 human mast cell line and in cord bloodderived human mast cells. Immunocytochemistry was used to localize OSM in human mast cells, and its biologic activity was verified by its effect on the proliferation of human lung fibroblasts.
OSM was expressed and released specifically on T cellinduced mast cell activation but not on IgE cross-linking. OSM was localized to the cytoplasm, and its expression was inhibited by dexamethasone and mitogen-activated protein kinase inhibitors. OSM was also found to be biologically active in inducing lung fibroblast proliferation that was partially but significantly inhibited by anti-OSM mAb. In vivo mast cells were found to express OSM in both biopsy specimens and bronchoalveolar lavage fluid from patients with sarcoidosis.
The production of OSM by human mast cells might represent one link between T cellinduced mast cell activation and the development of a spectrum of structural changes in T cellmediated inflammatory processes in which mast cells have been found to be involved.
Mast cells might serve as a target for treating T cellmediated fibrotic processes.
Key words: Oncostatin M; mast cells; T cells
Abbreviations: BAL, Bronchoalveolar lavage; CBMC, Cord blood mast cell; ERK, Extracellular signal-regulated kinase; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; JNK, Jun N-terminal kinase; MAPK, Mitogen-activated protein kinase; OSM, Oncostatin M; PMA, Phorbol 12-myristate 13-acetate; QR-PCR, Quantitative real-time PCR; SCF, Stem cell factor; Tc-m, Nonactivated Jurkat T-cell membrane; Tc*-m, Activated Jurkat T-cell membrane
Supported in part by a research grant from the Israel Science Foundation, founded by the Israel Academy of Sciences and Humanities, and by the Frederick Reiss chair in dermatology, Tel Aviv University.Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.
Reprint requests: Yoseph A. Mekori, MD, Department of Medicine B, Meir General Hospital, Kfar Saba 44281, Israel.
* These two authors contributed equally to this work.