To verify the hypothesis that alveolar macrophages (AMs) from patients infected with HIV-1 could synthesize and release TNFα, AMs recovered from the BAL fluid of 11 patients with seropositive HIV-1 (six with AIDS and five with ARC) were tested in vitro for their ability to destroy TNFα-susceptible targets. Furthermore, the presence of TNFα was assessed in AM-conditioned supernatants on the basis of their cytotoxic activity and by using an immunoenzymatic test and immunoblotting. Transcription of the TNFα gene in AMs was also studied by means of the Northern blot analysis. AMs freshly recovered from patients infected with HIV-1 exhibited high levels of cell-mediated cytotoxicity against U937 targets, and the addition of a polyclonal anti-TNFα antibody resulted in a significant inhibition of the target lysis. Cell-free supernatants conditioned by unstimulated AMs exerted high levels of cytotoxic activity against TNFα-sensitive targets, whereas duplicate, neutralization experiments performed in the presence of an anti-TNFα antibody proved that the observed cytotoxic activity was mostly mediated by TNFα. The presence of high amounts of TNFα in the conditioned media was confirmed by the immunoenzymatic test. In addition, the immunoblot analysis showed that the TNFα released by AMs has a M(r) 17,000 band, identical to a standard preparation of recombinant TNFα. The Northern blot demonstrated that unstimulated AMs express detectable levels of mRNA transcripts for TNFα. Taken together, our data support the concept that AMs from patients with HIV-1 infection constitutively release TNFα. Because normal human AMs do not express detectable levels of mRNA for TNFα or release this cytokine, the hypothesis is formulated that in the lung of patients with AIDS, AMs, either by a direct effect of HIV-1 infection or as a consequence of the pulmonary opportunistic infections, are triggered to synthesize TNFα. This in situ overproduction might play a role in the pathogenesis of AIDS-related pulmonary complications.
|Number of pages||7|
|Journal||American Review of Respiratory Disease|
|Publication status||Published - 1991|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine