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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sørensen, O. E. Articles by Borregaard, N. Search for Related Content PubMed PubMed Citation Articles by Sørensen, O. E. Articles by Borregaard, N. Related Collections Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2001, Vol. 97, No. 12, pp. 3951-3959 PHAGOCYTES Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3 Ole E. Sørensen, Per Follin, Anders H. Johnsen, Jero Calafat, G. Sandra Tjabringa, Pieter S. Hiemstra, and Niels Borregaard From the Granulocyte Research Laboratory, Departments of Hematology and Clinical Biochemistry, Copenhagen University Hospital, Denmark; the Department of Infectious Diseases, Linköping University, Sweden; the Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands; and the Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no detectable cleavage of hCAP-18 in cells after phagocytosis. In contrast, hCAP-18 was cleaved to generate LL-37 in exocytosed material. Of the 3 known serine proteases from azurophil granules, proteinase 3 was solely responsible for cleavage of hCAP-18 after exocytosis. This is the first detailed study describing the generation of a human antimicrobial peptide from a promicrobicidal protein, and it demonstrates that the generation of active antimicrobial peptides from common proproteins occurs differently in related species. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Soehnlein, A. Zernecke, E. E. Eriksson, A. G. Rothfuchs, C. T. Pham, H. Herwald, K. Bidzhekov, M. E. Rottenberg, C. Weber, and L. Lindbom Neutrophil secretion products pave the way for inflammatory monocytes Blood, August 15, 2008; 112(4): 1461 - 1471. [Abstract] [Full Text] [PDF] R. Bucki, D. B. Namiot, Z. Namiot, P. B. Savage, and P. A. Janmey Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13 J. Antimicrob. Chemother., August 1, 2008; 62(2): 329 - 335. 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