Alveolar macrophages from subjects infected with HIV-1 express macrophage inflammatory protein-1 alpha (MIP-1 alpha): contribution to the CD8+ alveolitis.
We examined the synthesis and release of MIP-1 alpha in alveolar macrophages obtained from normal subjects or subjects infected with HIV-1, at different stages of the disease. HIV-1-infected subjects in groups II, III and IV all had significant interstitial pneumonitis, featuring a significant infiltration of CD8+ lymphocytes in the bronchoalveolar lavage. Alveolar macrophages from HIV-1-infected subjects were shown to express significant levels of MIP-1 alpha via immunohistochemistry, both spontaneously and in response to lipopolysaccharide (LPS), whereas cells from normal subjects expressed very low levels of the cytokine. Supernatants of alveolar macrophages from HIV-1-infected subjects exerted strong chemotactic activity for purified activated blood CD8+ T lymphocytes, which was strongly inhibited by neutralizing MIP-1 alpha. Studies of patients with HIV-1 infection at different stages of the disease showed that MIP-1 alpha secretion increased as viral infection developed. There was a significant positive correlation between MIP-1 alpha secretion and the CD8+ alveolitis in HIV-1-infected subjects. Infection of alveolar macrophages in vitro with three distinct strains of HIV-1 which replicated profusely in macrophages did not induce the expression of MIP-1 alpha. Collectively, these data suggest that HIV-1 infection in vivo induces MIP-1 alpha expression and release in alveolar macrophages, and this appears to contribute significantly to the alveolar lymphocytosis seen in HIV-1-infected subjects.
Denis
M
M
Pulmonary Research Unit, Faculty of Medicine, University of Sherbrooke, Canada.
Ghadirian
E
E
D000328:Adult; D000542:Alveolitis, Extrinsic Allergic / Q000209:etiology*; D016827:CD8 Antigens / Q000276:immunology*; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D015846:Monokines / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets
D016827:CD8 Antigens; D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines