Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis
Title | Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Liu, QN, Reddy, S, Sayre, JW, Pop, V, Graves, MC, Fiala, M |
Journal | AIDS Research and Human Retroviruses |
Volume | 17 |
Issue | 15 |
Pagination | 1423-33 |
Date Published | 10/2001 |
Keywords | Cyclooxygenase 2, External, Isoenzymes, Kidney, Left, Leukocytes, Lymphocyte Activation, Macrophage Activation, Myocarditis, Nitric Oxide Synthase Type II, Prostaglandin-Endoperoxide Synthases, T-Lymphocytes, Ventricular Dysfunction |
Abstract | HIV-1 cardiomyopathy has become a major cause of death in AIDS patients, but its pathogenesis is unclear. We used an antigen retrieval technique and immunostaining to investigate the hearts of 15 AIDS patients, of whom 3 had dilated cardiomyopathy. Immunocytochemistry shows infiltration of the left ventricular myocardium with mononuclear cells, ranging from minimal to diagnostic of myocarditis. The infiltrates include macrophages and CD3(+) and CD8(+) T cells. The tight junction protein ZO-1 is disrupted at the site of monocyte-macrophage vascular penetration and the coronary vessels show fibrinogen leakage in the hearts of AIDS patients, but not in the normal heart. A subset of infiltrating macrophages is doubly positive for cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase. HIV-1 peptides gp120 and Nef are expressed in macrophages and T cells, but not in cardiomyocytes. COX-2 is expressed by both gp120-positive and gp120-negative macrophages. The hearts of AIDS patients separate into those showing minimal infiltrates with low COX-2 expression and those with dense infiltrates and high COX-2; all failing hearts are in the latter group. These data suggest that COX-2-activated and HIV-1-infected monocyte-macrophages and T cells play a crucial role in the progression of HIV-1 myocarditis to HIV-1 cardiomyopathy. |
URL | http://www.ncbi.nlm.nih.gov/pubmed/11679155 |