Progression of HIV disease is associated with increased expression of FcγRI and CR1 on alveolar macrophages

Abstract

SUMMARYThe expression of receptors for complement and the Fc region of immunoglobulin by alveolar macrophages (AM) constitutes a valuable aid to effector function of these cells. However, during HIV infection such expression may also act to increase binding of immune complexes, thus facilitating viral infection of these cells. This study was designed to determine whether changes in the expression of these receptors occurs in situ during HIV infection. Lung macrophages were isolated by bronchoalveolar lavage in groups of HIV + subjects segregated on the basis of peripheral CD4 count. A group of normal subjects was also investigated. Expression of CR1 and FcgRI was quantified by measuring the optical density of reaction product following controlled immunoperoxidase staining with MoAbs CD35 and CD64. Both CR1 and FcgRI were increased over normal in all HIV + subjects. This increase was progressive with advancing disease as determined by correlation with declining peripheral CD4 count. Comparison of asymptomatic and symptomatic subjects with HIV infection showed no difference in CR1 expression but a rise in FcgRI expression in the latter group. An overall inverse correlation was also found between peripheral CD4 count and FcgRI expression, but not CR1 expression. These data demonstrate a significant increase in the expression of these receptors on AM from HIV + subjects, and show that this increase may occur before any symptoms in these patients.

Surfactant protein A enhances the phagocytosis of C1q-coated particles by alveolar macrophages

“…Tenner and coworkers (36) showed that SP-A functions as an activation ligand by stimulating complement receptor 1 (CR1)-mediated phagocytosis by monocytes and monocyte-derived macrophages. CR1 binds C1q (19), C3b, and C4b, and, unlike C1qR p , CR1 is expressed by AM (10,14). In the current study, SP-Aenhanced phagocytosis of C1q-coated particles could be due in part to upregulation of CR1 (or another C1q receptor) on AM.…”

A Soluble Mannose Receptor Immunoadhesin Enhances Phagocytosis of Pneumocystis carinii by Human Polymorphonuclear Leukocytes In Vitro

“…This assumption appears valid because the alveolar macrophage Fc-receptor function is not impaired in HIV-infection [16]. In some cases alveolar macrophages of HIV-infected patients show increased Fc-receptor expression and enhanced phagocytic function [29,30].…”

Pulmonary Innate Immune Dysfunction in Human Immunodeficiency Virus

“…Importantly, the virus can primarily infect macrophages, which, in turn, act as a reservoir for the virus (14). Although many mechanisms of macrophage infection have been described, in the alveolar macrophage in particular, HIV infection up-regulates expression of FcgRI and complement receptor 1, and these two surface molecules then act as facilitators of HIV entry into cells (15). Other studies have implicated the viral protein, Vpr, in the infection of human macrophages and enhancement of viral replication (16).…”