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Proteases as Targets for Therapy pp 259–275Cite as

Serine Elastases in Inflammatory and Vascular Diseases

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 140))

Abstract

Elastase is a general term that has traditionally described a group of proteinases that have the ability to degrade elastin, the primary extracellular matrix (ECM) protein that confers elastic qualities to a variety of tissues, including the lungs, skin and blood vessels. Different proteinases from the serine, cysteine and metallo classes have been shown to degrade elastin with varying degrees of activity. Of these different classes of proteinases, other than the metalloproteinase metalloelastase [matrix metalloprotein 12 (MMP-12) (SHAPIRO 1994; GRONSKI et al. 1997; MECHAM et al. 1997)], the serine elastases — pancreatic elastase (PE), neutrophil elastase (NE), proteinase-3 (PR-3) — have been the subject of the most intensive investigations thus far. These three enzymes have been characterized extensively, and their crystal structures have been elucidated and published. Two additional enzymes [endogenous vascular elastase (EVE) and endothelial cell elastase (ECE)] are, as yet, less well characterized and have only been identified as having “elastase-like” activities based on substrate and inhibitor activity profiles, although EVE has been shown to degrade insoluble elastin (BUSSOLINO et al. 1994; ZHU et al. 1994). Finally, at least three other serine elastases, as defined by their substrate/inhibition profiles, have been described; these were derived from transformed rat- liver epithelial or Schwann cells, human carcinoma cell lines (CAPPELLUTI and HARRIS 1994), human skin fibroblasts (CROUTE et al. 1991) and human lymphocytes (PACKARD et al. 1995). The relationships of these enzymes to PE, NE, PR-3, EVE and ECE are not known. This review will focus on NE, PR-3, EVE and, to a lesser extent, ECE, with respect to their potential roles in inflammatory and vascular diseases.

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  1. Source Precision Medicine, Drug Discovery and Development, 2425 N. 55th Street, Suite,111, Boulder, CO, 80301, USA

    J. C. Cheronis (Vice President)

  2. Laboratory Medicine and Pathobiology, and Cardiovascular Research, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada

    M. Rabinovitch

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  1. Max-von-Pettenkofer Institut für medizinische Mikrobiologie, LM Universität, LS Virologie Pettenkoferstr. 9a, D-80336, München, Germany

    Klaus von der Helm Ph.D., M.D.

  2. DuPont Pharmaceutical Co Research and Development, Edperimental Station, E336/31B, Wilmington, DE, 19880-0336, USA

    Bruce D. Korant Ph.D.

  3. Drug Discovery and Development, Source Precision Medicine, 2425 N. 55th Street, Suite 111, Boulder, CO, 80301, USA

    John C. Cheronis M.D., Ph.D. (Vice President) (Vice President)

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Cheronis, J.C., Rabinovitch, M. (2000). Serine Elastases in Inflammatory and Vascular Diseases. In: von der Helm, K., Korant, B.D., Cheronis, J.C. (eds) Proteases as Targets for Therapy. Handbook of Experimental Pharmacology, vol 140. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57092-6_14

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