Mycobacterium tuberculosis induces secretory leukocyteproteinase inhibitor (SLPI) production by human macrophages

PASQUINELLI, V; TATEOSIAN, NANCY; QUIROGA, M; MARTINEZ, G; JURADO, J; CHULUYAN, E; GARCIA, V

Cordoba, Argentina

Congreso; VII Latin American Congress of Immunology; 2005

SAI

One-third of the world’s population is infected with Mycobacterium tuberculosis, a bacteria that causes disease in up to 10 million people annually worldwide. During the course of infection with M. tuberculosis, innate immune responses control the spread of the bacteria, but T lymphocyte recruitment to the lung is required for containment of M. tuberculosis in granulomas. The interaction of mycobacteria with antigen presenting cells is a key feature in the pathogenesis of tuberculosis and the outcome of this interaction is pivotal in determining whether immunity or disease ensues. Human and mouse macrophages have been shown to become infected with mycobacteria and to produce a response to infection that reflects their suggested role in immunity. Thus, macrophages elicit anti-microbial mechanisms for elimination of mycobacteria. Secretory leukocyte proteinase inhibitor (SLPI) is a protease inhibitor purified from different sources, including lung secretions (Sallenave J-M. Respir Res 1:87, 2000). The role of this serpin in inflammatory cells such as macrophages is uncertain, although antibacterial or anti-inflammatory actions were proposed (Sallenave J-M. Bioch Soc 30:111, 2002). Neutrophil elastase (NE) is the most important protease of the human lung; if not inhibited NE is able to attack nearly all structural proteins and components of the immune system of the lung (Vogelmeier C. et al. Pneumunol 48:57, 1994). In the normal human lung this is prevented by an excess of protease inhibitors. Furthermore, to migrate from the vascular space and gain access to the inflammatory site through the interstitium, it has been hypothesized that inflammatory cells use a variety of proteases. To contain the potential injurious effects of excess release of these proteases, the host secretes large amounts of antiproteinases (Sallenave J-M. Respir Res 1:87, 2000). They are synthesized and secreted locally at the site of injury and are produced in response to primary cytokines such as IL-1 and TNF-a; they might therefore be part of a first wave of local, inducible defense in the antiproteinases network. In Acute respiratory distress syndrome (ARDS) and pneumonia, SLPI is markedly increased in bronchoalveolar lavage (BAL) fluid compared with control subjects. Interestingly, SLPI BAL levels were positively correlated with the multiple organ failure score suggesting that antiproteases such as SLPI might be released in this pathology as an aborted and unsuccessful attempt to control injury. Furthermore, in patients with pneumonia, SLPI levels were found to be increased in serum, which is consistent with the hypothesis that these inhibitors are ‘alarm inhibitors’ whose role might be relevant at the onset of the inflammatory process (Sallenave J-M. Respir Res 1:87, 2000).