%0 Journal Article %1 Valenzuela2013 %A Valenzuela, N. M. %A Hong, L. %A Shen, X-Da %A Gao, F. %A Young, S. H. %A Rozengurt, E. %A Kupiec-Weglinski, J. W. %A Fishbein, M. C. %A Reed, E. F. %D 2013 %J Am J Transplant %K mucosal epithelial tlymphocytes bcells %N 2 %P 299--311 %R 10.1111/ajt.12016 %T Blockade of p-selectin is sufficient to reduce MHC I antibody-elicited monocyte recruitment in vitro and in vivo. %U http://dx.doi.org/10.1111/ajt.12016 %V 13 %X Donor-specific HLA antibodies significantly lower allograft survival, but as yet there are no satisfactory therapies for prevention of antibody-mediated rejection. Intracapillary macrophage infiltration is a hallmark of antibody-mediated rejection, and macrophages are important in both acute and chronic rejection. The purpose of this study was to investigate the Fc-independent effect of HLA I antibodies on endothelial cell activation, leading to monocyte recruitment. We used an in vitro model to assess monocyte binding to endothelial cells in response to HLA I antibodies. We confirmed our results in a mouse model of antibody-mediated rejection, in which B6.RAG1(-/-) recipients of BALB/c cardiac allografts were passively transferred with donor-specific MHC I antibodies. Our findings demonstrate that HLA I antibodies rapidly increase intracellular calcium and endothelial presentation of P-selectin, which supports monocyte binding. In the experimental model, donor-specific MHC I antibodies significantly increased macrophage accumulation in the allograft. Concurrent administration of rPSGL-1-Ig abolished antibody-induced monocyte infiltration in the allograft, but had little effect on antibody-induced endothelial injury. Our data suggest that antagonism of P-selectin may ameliorate accumulation of macrophages in the allograft during antibody-mediated rejection.

@article{Valenzuela2013, abstract = {Donor-specific HLA antibodies significantly lower allograft survival, but as yet there are no satisfactory therapies for prevention of antibody-mediated rejection. Intracapillary macrophage infiltration is a hallmark of antibody-mediated rejection, and macrophages are important in both acute and chronic rejection. The purpose of this study was to investigate the Fc-independent effect of HLA I antibodies on endothelial cell activation, leading to monocyte recruitment. We used an in vitro model to assess monocyte binding to endothelial cells in response to HLA I antibodies. We confirmed our results in a mouse model of antibody-mediated rejection, in which B6.RAG1(-/-) recipients of BALB/c cardiac allografts were passively transferred with donor-specific MHC I antibodies. Our findings demonstrate that HLA I antibodies rapidly increase intracellular calcium and endothelial presentation of P-selectin, which supports monocyte binding. In the experimental model, donor-specific MHC I antibodies significantly increased macrophage accumulation in the allograft. Concurrent administration of rPSGL-1-Ig abolished antibody-induced monocyte infiltration in the allograft, but had little effect on antibody-induced endothelial injury. Our data suggest that antagonism of P-selectin may ameliorate accumulation of macrophages in the allograft during antibody-mediated rejection.}, added-at = {2013-04-12T04:25:31.000+0200}, author = {Valenzuela, N. M. and Hong, L. and Shen, X-Da and Gao, F. and Young, S. H. and Rozengurt, E. and Kupiec-Weglinski, J. W. and Fishbein, M. C. and Reed, E. F.}, biburl = {https://www.bibsonomy.org/bibtex/2ff57c25b86d9b0f123b39cfdfa752066/aorchid}, doi = {10.1111/ajt.12016}, file = {:allorejection/AmJTransplant.13.299.pdf:PDF}, groups = {public}, institution = {Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.}, interhash = {f38461cc2a51ed06a1d15ca3bafd21cf}, intrahash = {ff57c25b86d9b0f123b39cfdfa752066}, journal = {Am J Transplant}, keywords = {mucosal epithelial tlymphocytes bcells}, language = {eng}, medline-pst = {ppublish}, month = Feb, number = 2, pages = {299--311}, pmid = {23279566}, timestamp = {2013-04-12T04:25:31.000+0200}, title = {Blockade of p-selectin is sufficient to reduce MHC I antibody-elicited monocyte recruitment in vitro and in vivo.}, url = {http://dx.doi.org/10.1111/ajt.12016}, username = {aorchid}, volume = 13, year = 2013 }