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Secretory Leukocyte Protease Inhibitor and Elafin/Trappin-2

Versatile Mucosal Antimicrobials and Regulators of Immunity

¹ Institut Pasteur, Unité de Défense Innée et Inflammation, Paris, France; and ² INSERM, U874, Paris, France

Correspondence and requests for reprints should be addressed to Jean-Michel Sallenave, Ph.D., Institut Pasteur, Unité de Défense Innée et Inflammation, F-75015, Paris, France. E-mail: jms{at}pasteur.fr

Abstract

Elafin and secretory leukocyte protease inhibitor (SLPI) are pleiotropic molecules chiefly synthesized at the mucosal surface that have a fundamental role in the surveillance against microbial infections. Their initial discovery as anti-proteases present in the inflammatory milieu in chronic pathologies such as those of the lung suggested that they may play a role in keeping in check extracellular proteases released during the excessive activation of innate immune cells such as neutrophils. This soon proved to be a simplistic explanation, as other functions were also soon ascribed to these molecules (antimicrobial, modulation of innate and adaptive immunity, regulation of tissue repair). Data emanating from patients with chronic pathologies (in the lung and elsewhere) have shown that SLPI and elafin are often inactivated in inflammatory secretions, either through the action of host or microbial products, justifying attempts at antiprotease supplementation in clinical protocols. Although these have been sparse, proof of principle has been demonstrated, and future challenges will undoubtedly rest with improvements in methods of delivery in the context of tissue inflammation and in careful selection of patients more likely to benefit from SLPI/elafin augmentation.

Key Words: inflammation • immunity • lung • secretory lekocyte protease inhibitor • elafin

CLINICAL RELEVANCE Despite the inherent difficulties of targetting drugs to the inflammed lungs, the very pleiotropic activity of secretory leukocyte protease inhibitor and elafin (antibacterial, adjuvanticity at mucosal defences, anti-protease) suggest that these molecules should be of interest to pharmaceutical companies and pulmonologists seeking solutions to treat infective exacerbations of inflammatory lung diseases.