Upregulation of Chitinase 1 in Alveolar Macrophages of HIV-Infected Smokers

Recent studies suggest that HIV-1 infection is an independent risk factor for the development of COPD and lung cancer. We hypothesized that HIV infection and cigarette smoking synergize to alter the function of alveolar macrophages (AMs). To test this hypothesis, transcriptome analysis was performed on purified AMs from 20 individuals split evenly between HIV-infected and -uninfected and smokers and nonsmokers. Differential expression analysis identified 143 genes significantly altered by the combination of HIV infection and smoking. Of the differentially expressed genes, chitinase 1 (CHIT1) and CYP1B1, both previously associated with COPD, were upregulated 3-fold and 10-fold, respectively, in the untreated HIV+ smoker cohort. Expression of CHIT1 and CYP1B1 correlated with the expression of genes involved in extracellular matrix organization, oxidative stress, immune response, and cell death. Likewise, CHIT1 protein levels were significantly upregulated in bronchoalveolar lavage (BAL) fluid from HIV-infected smokers, and increased CHIT1 levels were negatively correlated with lung function measurements. Overall, these findings raise the possibility that elevated CHIT1 is an early indicator of COPD development in HIV-infected smokers and that its level may serve as a biomarker for determining this risk.