Expression and use of human immunodeficiency virus type 1 coreceptors by human alveolar macrophages

Human immunodeficiency virus type 1 (HIV-1) requires, in addition to CD4, c oreceptors of the CC or CXC chemokine families for productive infection of T cells and cells of the monocyte-macrophage lineage. Based on the hypothes is that coreceptor expression on alveolar macrophages (AM) may influence HI V-1 infection of AM in the lung, this study analyzes the expression and uti lization of HIV-1 coreceptors on AM of healthy individuals. AM were product ively infected with five different primary isolates of HIV-1. Levels of sur face expression of CCR5, CXCR4, and CD4 were low compared to those of blood monocytes, but CCR3 was not detectable. mRNA for CCR5, CXCR4, CCR2, and CC R3 were all detectable, but to varying degrees and with variability among d onors. Expression of CCR5, CXCR4, and CCR2 mRNA was downregulated following stimulation with lipopolysaccharide (LPS). In contrast, secretion of the c hemokines RANTES, MIP-1 alpha, and MIP-1 beta was upregulated with LPS stim ulation. Interestingly, HIV-1 replication was diminished following LPS stim ulation. Infection of AM with HIV-1 in the presence of the CC chemokines de monstrated blocking of infection. Together, these studies demonstrate that AM can be infected by a variety of primary HIV-1 isolates, AM express a var iety of chemokine receptors, the dominant coreceptor used for HIV entry int o AM is CCR5, the expression of these receptors is dependent on the state o f activation of AM, and the ability of HIV-1 to infect AM may be modulated by expression of the chemokine receptors and by chemokines per se.