Anti-MHC Class I Antibody Activation of Proliferation and Survival Signaling in Murine Cardiac Allografts.

Anti-MHC Class I Antibody Activation of Proliferation and Survival Signaling in Murine Cardiac Allografts. Research Abstract Details 

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Anti-MHC Class I Antibody Activation of Proliferation and Survival Signaling in Murine Cardiac Allografts. Abstract Text:

Peter T Jindra,Aileen Hsueh,Longshen Hong,David Gjertson,Xiu-Da Shen,Feng Gao,Julie Dang,Paul S Mischel,William M Baldwin,Michael C Fishbein,Jerzy W Kupiec-Weglinski,Elaine F Reed,

Anti-MHC class I alloantibodies have been implicated in the process of acute and chronic rejection because these Abs can bind to endothelial cells and transduce signals leading to the activation of cell survival and proliferation pathways. To characterize the role of the MHC class I-signaling pathway in the pathogenesis of Ab-mediated rejection, we developed a mouse vascularized heterotopic cardiac allograft model in which B6.RAG1 KO hosts (H-2K(b)/D(b)) received a fully MHC-incompatible BALB/c (H-2K(d)/D(d)) heart transplant and were passively transfused with anti-donor MHC class I Ab. We demonstrate that cardiac allografts of mice treated with anti-MHC class I Abs show characteristic features of Ab-mediated rejection including microvascular changes accompanied by C4d deposition. Phosphoproteomic analysis of signaling molecules involved in the MHC class I cell proliferation and survival pathways were elevated in anti-class I-treated mice compared with the isotype control-treated group. Pairwise correlations, hierarchical clustering, and multidimensional scaling algorithms were used to dissect the class I-signaling pathway in vivo. Treatment with anti-H-2K(d) Ab was highly correlated with the activation of Akt and p70S6Kinase (S6K). When measuring distance as a marker of interrelatedness, multidimensional scaling analysis revealed a close association between members of the mammalian target of rapamycin pathway including mammalian target of rapamycin, S6K, and S6 ribosomal protein. These results provide the first analysis of the interrelationships between these signaling molecules in vivo that reflects our knowledge of the signaling pathway derived from in vitro experiments.

Anti-MHC Class I Antibody Activation of Proliferation and Survival Signaling in Murine Cardiac Allografts. Publishing Authors By Initials

PT Jindra,A Hsueh,L Hong,D Gjertson,XD Shen,F Gao,J Dang,PS Mischel,WM Baldwin,MC Fishbein,JW Kupiec-Weglinski,EF Reed,

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Anti-MHC Class I Antibody Activation of Proliferation and Survival Signaling in Murine Cardiac Allografts. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 180

Page Numbers: 2214-24

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Feb

YEAR: 2008

Anti-MHC Class I Antibody Activation of Proliferation and Survival Signaling in Murine Cardiac Allografts. Information

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LANGUAGE: eng

NlmUniqueID: 2985117

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Grant and Affiliation Information for Anti-MHC Class I Antibody Activation of Proliferation and Survival Signaling in Murine Cardiac Allografts.

AFFILIATION: University of California Los Angeles (UCLA) Immunogenetics Center and.

Country: United States

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MEDLINETA: J Immunol

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