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Originally published online as doi:10.1189/jlb.0108001 on March 19, 2008

Published online before print March 19, 2008
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(Journal of Leukocyte Biology. 2008;83:1309-1322.)
© 2008 by Society for Leukocyte Biology

Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity

V. Shpacovitch*,1, M. Feld*, M. D. Hollenberg{dagger}, T. A. Luger* and M. Steinhoff*

* Department of Dermatology and Ludwig Boltzmann Institute for Cell Biology of the Skin, University of Münster, Münster, Germany; and
{dagger} Inflammation Research Network, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada

1Correspondence: Dept. of Dermatology, Laboratory of Cell Biology, University of Münster von-Esmarch-Str. 58, 48149 Münster, Germany. E-mail: shpacovi{at}ukmuenster.de

Serine proteases are well known as enzymes involved in digestion of dietary proteins, blood coagulation, and homeostasis. Only recent groundbreaking studies revealed a novel role of serine proteases as signaling molecules acting via protease-activated receptors (PARs). Important effects of PAR activation on leukocyte motility, cytokine production, adhesion molecule expression, and a variety of other physiological or pathophysiological functions have been described in vitro and in vivo. The crucial role of PAR activation during disease progression was revealed in animal models of different gastrointestinal pathologies, neuroinflammatory and neurodegenerative processes, skin, joint and airway inflammation, or allergic responses. This review focuses on the findings related to the impact of PAR deficiency in animal models of inflammatory and allergic diseases. Additionally, we observe the role of PAR activation in the regulation of functional responses of innate and adaptive immune cells in vitro. Understanding the mechanisms by which PARs exert the effects of serine proteases on immune cells may lead to new therapeutic strategies in inflammation, immune defense, and allergy.

Key Words: proteolytic enzymes • leukocytes • allergy • infectious diseases






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