Dysregulation of beta-chemokines in the lungs of HIV-1-infected patients

J Acquir Immune Defic Syndr. 2001 Apr 1;26(4):305-14. doi: 10.1097/00126334-200104010-00002.

Abstract

The beta-chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, monocyte chemotactic protein (MCP)-1 and regulated-on-activation normal T cell, expressed and secreted (RANTES) are not only chemotactic for mononuclear cells but may be important in suppression of HIV-1 replication through competitive binding to the chemokine receptor, CCR5, which is critical to viral entry. In this study, bronchoalveolar cells (BACs) and autologous peripheral blood mononuclear cells (PBMCs) were obtained from HIV-1-infected participants who did not manifest clinical signs of lung disease with peripheral CD4 T-cell count >200/mm(3) (n = 7, group with high CD4 count), or CD4 T-cell count <200/mm(3) (n = 12, group with low CD4 count), and from healthy study subjects (n = 5). The capacity to express beta-chemokines and CCR5 was assessed. Induction of MIP-1 alpha by lipopolysaccharide (LPS) in BAC of HIV-1-infected study subjects from the low CD4 group was less than BAC from healthy study subjects (p <.001), and also was less than in BACs from the group with a high CD4 group (p <.001). Moreover, the intracellular expression of MIP-1 alpha in LPS-induced monocytes of HIV-1-infected patients was significantly less than that from healthy study subjects (p <.01). In addition, spontaneous expression of mRNAs for CCR5 and MIP-1 alpha in BAC was significantly lower in HIV-1-infected patients compared with in healthy study subjects (p <.03 and p <.02, respectively). In contrast to the findings with MIP-1 alpha, LPS stimulated MCP-1 in BAC from the group of HIV-1-infected patients with high CD4 count was significantly higher than healthy study subjects (p <.001). These dysregulations in the ability to express beta-chemokines by BAC may be important in the progression of HIV-1 infection in the lung.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bronchoalveolar Lavage
  • CD4 Lymphocyte Count
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Chemokine CCL4
  • Chemokine CCL5 / metabolism
  • Chemokines, CC / genetics
  • Chemokines, CC / metabolism*
  • Disease Progression
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • HIV Infections / pathology
  • Humans
  • Lipopolysaccharides / pharmacology
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism*
  • Lung / virology
  • Macrophage Inflammatory Proteins / genetics
  • Macrophage Inflammatory Proteins / metabolism
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Nuclease Protection Assays
  • Phytohemagglutinins / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR5 / genetics

Substances

  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines, CC
  • Lipopolysaccharides
  • Macrophage Inflammatory Proteins
  • Phytohemagglutinins
  • RNA, Messenger
  • Receptors, CCR5