Endothelial injury, alarmins, and allograft rejection.
Allograft blood vessels are important targets of clinical allograft rejection. Perioperative allograft injury to graft vasculature, especially the endothelial cell (EC) lining, increases the risk of subsequent acute and chronic vascular rejection. We hypothesize that allograft EC injured by ischemia-reperfusion (I/R) during transplantation releases mediators, termed "alarmins," that alter and intensify the host antigraft adaptive immune response. We begin with a review of both perioperative I/R injury to graft endothelium and T-cell-mediated vascular rejection. We then describe several alarmins that may be released from injured allografts, including interleukin (IL)-1alpha, ATP, monosodium urate (MSU), and high mobility group protein B1 (HMGB1). These mediators have in common the ability to induce production of IL-1beta from mononuclear phagocytes, and both isoforms of IL-1 act on T cells to enhance destructive adaptive immune responses. Therefore, we propose that IL-1 is the key alarmin that communicates graft injury to the host's adaptive immune system, and we suggest that perioperative targeting of IL-1 represents a promising strategy to attenuate the strength of rejection reactions.
Rao
Deepak A
DA
Department of Immunobiology, Section of Human and Translational Immunology, Yale University School of Medicine, New Haven, CT 06520-8089, USA.
Pober
Jordan S
JS
D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D024243:HMGB1 Protein / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014181:Transplantation Immunology / Q000276:immunology; D014527:Uric Acid / Q000276:immunology / Q000378:metabolism
D024243:HMGB1 Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D014527:Uric Acid