Lipid raft facilitated ligation of K-alpha1-tubulin by specific antibodies on epithelial cells: Role in pathogenesis of chronic rejection following human lung transplantation.

Biochemical and Biophysical Research Communications
Venkataswarup TiriveedhiT Mohanakumar

Abstract

Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-alpha1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients who develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4+/-1.1-, 3.2+/-0.9-, and 3.4+/-1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the g...Continue Reading

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Citations

Apr 23, 2011·Clinics in Chest Medicine·Christiane Knoop, Marc Estenne
Jan 3, 2016·Cellular Immunology·Suneetha AmaraVenkataswarup Tiriveedhi
Mar 21, 2018·Heart and Vessels·Zuzanna Podemska-JedrzejczakBartlomiej Perek
Apr 11, 2012·International Journal of Immunogenetics·V TiriveedhiT Mohanakumar
Jul 25, 2012·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·V TiriveedhiT Mohanakumar
Sep 1, 2015·Current Transplantation Reports·Vrushali V Agashe, William J Burlingham
Aug 14, 2012·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·F L KellyS M Palmer
Nov 2, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·J A SullivanW J Burlingham
Feb 7, 2017·Journal of Immunology Research·Ankit Bharat, T Mohanakumar

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