Interferon-gamma drives the metalloproteinase-dependent cleavage of HLA class I soluble forms from primary human bronchial epithelial cells. Hum Immunol 2002 Oct;63(10):893-901
Date
10/09/2002Pubmed ID
12368042DOI
10.1016/s0198-8859(02)00461-5Scopus ID
2-s2.0-0036775024 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
Activation of bronchial epithelial cells (BEC) and disruption of an intact epithelial barrier in a lung transplant recipient can lead to acute or chronic rejection, events that are associated with release of soluble human leukocyte antigen (sHLA) class I. Although we know that HLA is released from mitogen-activated lymphocytes in a metalloproteinase (MPase)-dependent fashion, the mechanism of release from nonlymphoid tissue is not well understood. To this end, we stimulated primary BEC with increasing amounts of the T-helper cell-1 cytokines, interferon gamma (IFNgamma), and/or tumor necrosis factor alpha (TNFalpha) and measured the quantity and forms of HLA class I release. We found that IFNgamma, but not TNFalpha, was able to stimulate a time- and concentration-dependent release of HLA/beta(2)m and beta(2)m-free heavy chain (HC) from the BEC. A portion (50%) of the HLA/beta(2)m release and >90% of the beta(2)m-free HC release was mediated by a MPase. Western blot analysis supported the conclusion that a MPase-sensitive pathway produced 36 and 37 kDa cleaved forms, whereas the secreted 39 kDa form of beta(2)m-associated soluble HLA class I (sHLA/beta(2)m) was MPase-resistant. This adds to the growing understanding of the extracellular processing pathways of major histocompatibility complex class I that may be critical for both chronic rejection as well as immune regulation.
Author List
Haynes LD, Bushkin Y, Love RB, Burlingham WJMESH terms used to index this publication - Major topics in bold
BronchiCells, Cultured
Dose-Response Relationship, Drug
Epithelial Cells
Histocompatibility Antigens Class I
Humans
Interferon-gamma
Metalloendopeptidases
Tumor Necrosis Factor-alpha
