Expression and use of human immunodeficiency virus type 1 coreceptors by human alveolar macrophages. Academic Article uri icon

Overview

MeSH

  • Antigens, CD4
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Gene Expression
  • Humans
  • Macrophage Activation
  • Macrophage Inflammatory Proteins
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CXCR4
  • Virus Replication

MeSH Major

  • HIV-1
  • Macrophages, Alveolar
  • Receptors, Chemokine
  • Receptors, HIV

abstract

  • Human immunodeficiency virus type 1 (HIV-1) requires, in addition to CD4, coreceptors of the CC or CXC chemokine families for productive infection of T cells and cells of the monocyte-macrophage lineage. Based on the hypothesis that coreceptor expression on alveolar macrophages (AM) may influence HIV-1 infection of AM in the lung, this study analyzes the expression and utilization of HIV-1 coreceptors on AM of healthy individuals. AM were productively infected with five different primary isolates of HIV-1. Levels of surface 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 CCR3 were all detectable, but to varying degrees and with variability among donors. Expression of CCR5, CXCR4, and CCR2 mRNA was downregulated following stimulation with lipopolysaccharide (LPS). In contrast, secretion of the chemokines RANTES, MIP-1alpha, and MIP-1beta was upregulated with LPS stimulation. Interestingly, HIV-1 replication was diminished following LPS stimulation. Infection of AM with HIV-1 in the presence of the CC chemokines demonstrated blocking of infection. Together, these studies demonstrate that AM can be infected by a variety of primary HIV-1 isolates, AM express a variety of chemokine receptors, the dominant coreceptor used for HIV entry into AM is CCR5, the expression of these receptors is dependent on the state of 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.

publication date

  • July 1999

has subject area

  • Antigens, CD4
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Gene Expression
  • HIV-1
  • Humans
  • Macrophage Activation
  • Macrophage Inflammatory Proteins
  • Macrophages, Alveolar
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, Chemokine
  • Receptors, HIV
  • Virus Replication

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC112647

PubMed ID

  • 10364338

Additional Document Info

start page

  • 5865

end page

  • 5874

volume

  • 73

number

  • 7