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 macro phages 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 ail had significant interstitial pneumonitis, featuring a significant infiltration of CD8(+) lymphocytes in the bronchoalveol ar lavage. Alveolar macrophages from HIV-1-infected subjects were show n to express significant levels of MIP-1 alpha via immunohistochemistr y, both spontaneously and in response to lipopolysaccharide (LPS), whe reas cells from normal subjects expressed very low levels of the cytok ine. 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 a lpha. Studies of patients with HIV-1 infection at different stages of the disease showed that MIP-1 alpha secretion increased as viral infec tion developed. There was a significant positive correlation between M IP-1 alpha secretion and the CD8(+) alveolitis in HIV-1-infected subje cts. Infection of alveolar macrophages in vitro with three distinct st rains of HIV-1 which replicated profusely in macrophages did not induc e 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.