Activation of alveolar macrophages in asymptomatic HIV-infected individuals

R. Buhl, H. A. Jaffe, K. J. Holroyd, Z. Borok, J. H. Roum, A. Mastrangeli, F. B. Wells, M. Kirby, C. Saltini, Ronald Crystal

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Abstract

After the initial infection with HIV, there is evidence of immune dysfunction despite an apparent normal clinical state. In the context that the lung is a major site affected by opportunistic infection during the progression of this immune dysfunction, and that some components of the immune system are activated during early HIV infection, we hypothesized that there may be activation of alveolar macrophages (AM), a key component of the pulmonary host defense system, during the asymptomatic phase of HIV infection. Compared to normals, in HIV-infected individuals the class II MHC molecules DR, DQ, and DP were all expressed more frequently and in greater cell surface density on AM (p < 0.03, all comparisons), and there was increased spontaneous release of superoxide anion (O(·)-2) by AM (p < 0.002). To gain insight into whether the activation of the AM was an inherent property of the cells or dependent on the in vivo milieu, AM were evaluated after 24 h in culture for O(·)-2 release. In contrast to the findings in fresh AM, after 24 h in culture, O(·)-2 release by HIV AM was not different from normals (p > 0.7), suggesting that these AM had been activated in vivo. To assess whether IFN-γ could be mediating these effects, mRNA levels of the IP-10 gene (a gene specifically induced by increased concentrations of IFN- γ) were quantified in AM. Strikingly, the IP-10 gene was expressed only in AM of HIV-seropositive individuals, suggesting the AM had been exposed to IFN-γ in vivo. Overall, these observations are consistent with the concept that the HIV-seropositive state is associated with activation of AM, in part due to local exposure to IFN-γ.

Original languageEnglish
Pages (from-to)1019-1028
Number of pages10
JournalJournal of Immunology
Volume150
Issue number3
Publication statusPublished - 1 Jan 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Buhl, R., Jaffe, H. A., Holroyd, K. J., Borok, Z., Roum, J. H., Mastrangeli, A., Wells, F. B., Kirby, M., Saltini, C., & Crystal, R. (1993). Activation of alveolar macrophages in asymptomatic HIV-infected individuals. Journal of Immunology, 150(3), 1019-1028.