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

V. PASQUINELLI; N. TATEOSIAN; F. QUIROGA; G. MARTÍNEZ; J. JURADO; E. CHULUYAN; V. GARCÍA

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología, ALAI 2005; 2005

ALAI

Mycobacterium tuberculosis INDUCES SECRETORY LEUKOCYTE PROTEINASE INHIBITOR (SLPI) PRODUCTION BY HUMAN MACROPHAGES Pasquinelli V, TATEOSIAN N, Quiroga MF, Martinez GJ, Jurado J,  chuluyan HE and Garcia VE. Department of Microbiology and Division of Immunogenetics, School of Medicine, UBA. Secretory leukocyte proteinase inhibitor (SLPI) is a protease inhibitor purified from different sources, including lung secretions. The role of this serpin in inflammatory cells such as macrophages is uncertain, although antibacterial or anti-inflammatory actions were proposed. Moreover, high levels of SLPI were detected in tuberculoid leprosy patients.  Here we investigated whether Mycobacterium tuberculosis (Mtb) might influence SLPI secretion in humans. Macrophages were differentiated from peripheral blood mononuclear cells from healthy donors during 5 days, in the presence/absence of GM-CSF.  Differentiated macrophages were then stimulated with Mtb for different times (from 24 hours to 5 days).  Supernatants were then assayed by ELISA. We found that Mtb induced SLPI production by macrophages differentiated with GM-CSF as early as 24 hours (1,14±0,29ng/ml).  Moreover, high levels of SLPI were secreted by GM-CSF differentiated macrophages at 2 days (1,85± 0,24ng/ml), reaching maximum levels at 5 days (2,12±0,86ng/ml).  However, when cells were differentiated in the absence of GM-CSF, secretion of SLPI was not detected until 4 days of Mtb stimulation (1,80±0.07ng/ml), indicating that these cells would require longer times to produce SLPI.  Our results show for the first time that Mtb induces SLPI secretion by human macrophages, and suggest that SLPI might function as an endogenous effector molecule of innate immunity, contributing to pathogen elimination without tissue damage.