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Proteases

  • J. A. Mahoney
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 158)

Abstract

The macrophage, as a gatekeeper to both the innate and acquired immune systems, has great potential as a therapeutic target for such diverse human disease states as bacterial and viral infection, autoimmunity, inflammatory diseases, and cancer. The phenotype of macrophages in different tissues varies markedly between tissues. While this characteristic creates technical challenges in terms of isolation and characterization of resident tissue macrophages, it opens the possibility of targeting individual tissue-specific macrophage populations for pharmacologic intervention. The proteases are among the most numerous and abundant of enzyme classes, representing 1%–4% of all proteins encoded by eukaryotic genomes. Proteases are particularly abundant in macrophages, where they are critical players in many key functions of the macrophage, such as degradation of exogenous, potentially pathogenic proteins; digestion of both foreign and self proteins into peptides for presentation by MHC class I and II; and functional regulation of target proteins, for example by removal of a regulatory domain or a transmembrane anchor. This chapter reviews some of the proteases expressed in macrophages, and discusses what functional roles have been shown for, or postulated for, these enzymes. The enzymes discussed here are divided into two main groups: ectoproteases, which cleave amino acids from either end of a protein or peptide, and endoproteases, which cleave proteins at internal sites. Examples are given illustrating the actions of proteases within the macrophage, at the cell surface, and after secretion into the extracellular milieu.

Keywords

Aminopeptidase Angiotensin converting enzyme Carboxypeptidase Caspase Cathepsin CPVL Matrix metalloprotease TNF-? converting enzyme 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • J. A. Mahoney
    • 1
  1. 1.Department of MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA

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