Dysregulation of beta-chemokines in the lungs of HIV-1-infected patients

The beta -chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, monocyte chemotactic protein (MCP)-1 and regulated-on-activation norm al T cell, expressed and secreted (RANTES) are not only chemotactic for mon onuclear cells but may be important in suppression of HIV-1 replication thr ough competitive binding to the chemokine receptor, CCR5, which is critical to viral entry. In this study, broncho alveolar cells (BACs) and autologou s peripheral blood mononuclear cells (PBMCs) were obtained from HIV-1-infec ted participants who did not manifest clinical signs of lung disease with p eripheral CD4 T-cell count > 200/mm(3) (n = 7, group with high CD4 count), or CD4 T-cell count < 200/mm3 (n = 12, group with low CD4 count), and from healthy study subjects (n = 5). The capacity to express beta -chemokines an d CCR5 was assessed. Induction of MIP-1 alpha by lipopolysaccharide (LPS) i n BAC of HIV-1-infected study subjects from the low CD4 group was less than BAC from healthy study subjects (p < .001), and also was less than in BACs from the group with a high CD4 group (p < .001). Moreover, the intracellul ar expression of MIP-1 alpha in LPS-induced monocytes of HIV-1-infected pat ients was significantly less than that from healthy study subjects (p < .01 ). In addition, spontaneous expression of mRNAs for CCR5 and MIP-la in BAC was significantly lower in HIV-1-infected patients compared with in healthy study subjects (p < .03 and p < .02, respectively). In contrast to the fin dings with MIP-1 alpha, LPS stimulated MCP-1 in BAC from the group of HIV-1 -infected patients with high CD4 count was significantly higher than health y study subjects (p < .001). These dysregulations in the ability to express beta -chemokines by BAC may be important in the progression of HIV-1 infec tion in the lung.