Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis.

Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis.
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HIV 1 型感染和环氧合酶 2 激活的巨噬细胞和 T 细胞在 HIV 1 型心肌炎中的重要作用。

DOI:
10.1089/088922201753197097
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发表时间:
2001
影响因子:
1.5
通讯作者:
Fiala,M
Fiala,M
中科院分区:
医学4区
文献类型:
--
作者:
Liu,QN;Reddy,S;Sayre,JW;Pop,V;Graves,MC;Fiala,M

文献摘要

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HIV-1型心肌病已成为艾滋病患者死亡的主要原因,但其发病机制尚不清楚。我们采用抗原回收技术和免疫染色对15例艾滋病患者的心脏进行了研究,其中3例为扩张型心肌病。免疫细胞化学示单核细胞浸润左心室心肌,范围从轻微到诊断性心肌炎。浸润物包括巨噬细胞、CD3+和CD8+T细胞。紧密连接蛋白ZO-1在单核-巨噬细胞血管渗透部位被破坏,艾滋病患者心脏冠状血管显示纤维蛋白原渗漏,而正常心脏没有。浸润性巨噬细胞的一个子集对环氧合酶2 (COX-2)和诱导型一氧化氮合酶双重阳性。HIV-1肽gp120和Nef在巨噬细胞和T细胞中表达,但在心肌细胞中不表达。COX-2在gp120阳性和gp120阴性巨噬细胞中均表达。艾滋病患者心脏分为浸润小、COX-2低表达型和浸润密集、COX-2高表达型;所有衰竭的心脏都属于后者。这些数据表明,cox -2激活和HIV-1感染的单核巨噬细胞和T细胞在HIV-1型心肌炎向HIV-1型心肌病的进展中起着至关重要的作用。
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.