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Up‐regulation of alveolar macrophage matrix metalloproteinases in HIV1+ smokers with early emphysema

HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1– smokers. Since human alveolar macrophages (AMs) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that up‐regulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. Microarray analysis was used to screen which matrix metalloproteinases (MMPs) genes were expressed by AM of HIV1+ smokers with early emphysema. For each of the MMP genes expressed (MMP‐1, −2, −7, −9, −10, −12 and −14), TaqMan PCR was used to quantify the relative expression in AM from four groups of individuals: HIV1– healthy nonsmokers, HIV1– healthy smokers, HIV1– smokers with early emphysema, and HIV1+ smokers with early emphysema. While AM gene expression of MMPs was higher in HIV1– individuals with emphysema in comparison with HIV1– healthy smokers, for the majority of the MMPs (−1, −7, −9, and −12), AM expression from HIV1+ smokers with early emphysema was significantly higher than in HIV1− smokers with early emphysema. HIV1+ individuals with early emphysema also had higher levels of epithelial lining fluid (ELF) MMPs (−2, −7, −9, and −12) than the 3 HIV1− groups. ELF MMP (−2,‐7,‐9, and −12) levels were similar in HIV1+ nonsmokers compared with HIV1− nonsmokers. Interestingly, the active forms of MMP‐2, −9, and −12 were exclusively detected in ELF from HIV1+ individuals with early emphysema. Since the activities of the up‐regulated AM MMPs include collagenases, gelatinases, matrilysins, and elastase, these data suggest that up‐regulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke.