| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,,||,
* Department of Immunology,
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland;
Stanford University Medical School, Stanford, CA 94305;
Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304;
¶ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093; and
|| Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602
Chemerin is an attractant for cells that express the serpentine receptor CMKLR1, which include immature plasmacytoid dendritic cells (pDC) and macrophages. Chemerin circulates in the blood where it exhibits low biological activity, but upon proteolytic cleavage of its C terminus, it is converted to a potent chemoattractant. Enzymes that contribute to this conversion include host serine proteases of the coagulation, fibrinolytic, and inflammatory cascades, and it has been postulated that recruitment of pDC and macrophages by chemerin may serve to balance local tissue immune and inflammatory responses. In this work, we describe a potent, pathogen-derived proteolytic activity capable of chemerin activation. This activity is mediated by staphopain B (SspB), a cysteine protease secreted by Staphylococcus aureus. Chemerin activation is triggered by growth medium of clinical isolates of SspB-positive S. aureus, but not by that of a SspBnull mutant. C-terminal processing by SspB generates a chemerin isoform identical with the active endogenous attractant isolated from human ascites fluid. Interestingly, SspB is a potent trigger of chemerin even in the presence of plasma inhibitors. SspB may help direct the recruitment of specialized host cells, including immunoregulatory pDC and/or macrophages, contributing to the ability of S. aureus to elicit and maintain a chronic inflammatory state.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants from the Polish Ministry of Scientific Research 2P04A07629 (to J.C.), 158/E-338/SPB/5.PR UE/DZ 19/2003 (to J.P.), and 2P04A01129 (to J.P. and G.D.), by a Fogarty International Research Collaborative Award R03TW007174-01 (to E.C.B. and J.C.), a grant from the Commission of the European Communities, Programme QLRT-2001-01250, the European Social Fund and National Budget in the Frame of The Integrated Regional Operational Programme (to G.D.). G.D. is a recipient of the Polish Science Foundation Scholarship for young scientists. B.A.Z., T.O., and E.C.B. were supported by National Institutes of Health Grants AI-59635 and GM-37734. S.J.A. was supported by a postdoctoral fellowship from the Cancer Research Institute, New York. T.M.H. was supported by Grant AI37113-09 from the National Institutes of Health.
2 P.K. and B.A.Z. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Joanna Cichy, Faculty of Biochemistry, Biophysics and Biotechnology, Ulica. Gronostajowa 7, 30-387 Krakow, Poland. E-mail address: Cichy{at}mol.uj.edu.pl
4 Abbreviations used in this paper: pDC, plasmacytoid dendritic cell; SspB, staphopain B; Spl, serine protease-like protein; ScpA, staphopain A; Aur, aureolysin; TFA, trifluoroacetic acid; MS, mass spectrometry.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
