CHEMOKINE PRODUCTION BY A HUMAN ALVEOLAR EPITHELIAL-CELL LINE IN RESPONSE TO MYCOBACTERIUM-TUBERCULOSIS

To investigate the role of chemokines during the initial local respons e to Mycobacterium tuberculosis in the human lung, we studied chemokin e production by the human alveolar epithelial cell line A549 after inf ection with M. tuberculosis. M. tuberculosis-infected A549 cells produ ced mRNAs and protein for monocyte chemotactic protein-1 (MCP-1) and i nterleukin-8 (IL-8) but not mRNAs for macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES. Chemokine production in response to M. tuberculosis was not dependent on production of tumor necrosis factor alpha, IL-1 beta, or IL-6. Two virulent clinical M. tu berculosis isolates, the virulent laboratory strain H37Rv, and the avi rulent strain H37Ra elicited production of comparable concentrations o f MCP-1 and IL-8, whereas killed M. tuberculosis and three Mycobacteri um avium strains did not. The three virulent M. tuberculosis strains g rew more rapidly than the avirulent M. tuberculosis strain in the alve olar epithelial cell line, and the three M. avium strains did not grow intracellularly. These findings suggest that intracellular growth is necessary for mycobacteria to elicit production of MCP-1 and IL-8 by a lveolar epithelial cells but that virulence and the rate of intracellu lar growth do not correlate with chemokine production. Alveolar epithe lial cells may contribute to the local inflammatory response in human tuberculosis by producing chemokines which attract monocytes, lymphocy tes, and polymorphonuclear cells.