title: Injury to allografts: innate immune pathways to acute and chronic rejection.
abstract: An emerging body of evidence suggests that innate immunity, as the first line of host defence against invading pathogens or their components [pathogen-associated molecular patterns, (PAMPs)], plays also a critical role in acute and chronic allograft rejection. Injury to the donor organ induces an inflammatory milieu in the allograft, which appears to be the initial key event for activation of the innate immune system. Injury-induced generation of putative endogenous molecular ligand, in terms of damage/danger-associated molecular patterns ("DAMPs") such as heat shock proteins, are recognized by Toll-like receptors (TLRs), a family of pattern recognition receptors on cells of innate immunity. Acute allograft injury (e.g. oxidative stress during donor brain-death condition, post-ischemic reperfusion injury in the recipient) induces "DAMPs" which may interact with, and activate, innate TLR-bearing dendritic cells (DCs) which, in turn, via direct allo-recognition through donor-derived DCs and indirect allo-recognition through recipient-derived DCs, initiate the recipient s adaptive alloimmune response leading to acute allograft rejection. Chronic injurious events in the allograft (e.g. hypertension, hyperlipidemia, CMV infection, administration of cell-toxic drugs [calcineurin-inhibitors]) induce the generation of "DAMPs", which may interact with and activate innate TLR-bearing vascular cells (endothelial cells, smooth muscle cells) which, in turn, contribute to the development of atherosclerosis of donor organ vessels (alloatherosclerosis), thus promoting chronic allograft rejection.
authors.affiliation: Baskent University, Ankara, Turkey, .
authors.forename: Walter G
authors.initials: WG
authors.lastname: Land