Mechanisms of immune-mediated myocyte injury.
Much progress has been made in defining the mechanisms by which altered systolic and diastolic function of the heart may be produced by components of the immune system activated during allograft rejection and myocarditis and in patients with dilated cardiomyopathy. It is clear that injury of the vascular bed can occur via both humoral and cellular mediators and probably accounts for the acute alterations in ventricular compliance that occur during allograft rejection, as well as the accelerated development of graft atherosclerosis. Altered myocyte function and lysis can be produced by CTL in vitro, but the importance of this injury process in vivo remains uncertain. Other cells present in the inflammatory infiltrate can also affect myocyte function and survival. Neutrophils may cause lysis of myocytes, and cytokines produced by infiltrating macrophages and HtL may reach a sufficient concentration in the interstitial microenvironment to decrease myocyte catecholamine responsiveness and/or directly depress myocyte contractility. Humoral antibodies to myocyte cell surface antigens may cause cell damage by an antibody-dependent cytotoxic cell mechanism or by directly binding to and altering sarcolemmal receptor and/or ion channel function. Further elucidation of the extent of involvement of these different mechanisms in specific clinical settings may provide a basis for improved therapy of immune-mediated cardiac injury and dysfunction.
Barry
W H
WH
Department of Medicine, University of Utah School of Medicine, Salt Lake City.
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016207:Cytokines