HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Richter, R. Articles by Forssmann, U. Search for Related Content PubMed PubMed Citation Articles by Richter, R. Articles by Forssmann, U.

Quantum Proteolytic Activation of Chemokine CCL15 by Neutrophil Granulocytes Modulates Mononuclear Cell Adhesiveness¹

Rudolf Richter^2,*, Roxana Bistrian, Sylvia Escher^*, Wolf-Georg Forssmann^*, Jalal Vakili, Reinhard Henschler, Nikolaj Spodsberg, Adjoa Frimpong-Boateng^* and Ulf Forssmann^*

^* IPF PharmaCeuticals GmbH, Hannover, Germany; Institute of Transfusion Medicine and Immune Hematology, Blood Donation Service of the German Red Cross, Frankfurt, Germany; and Institute of Interdisciplinary Research, Université Libre de Bruxelles, Brussels, Belgium; and Department of Medical Biochemistry and Genetics, The Panum Institute, Copenhagen, Denmark

Monocyte infiltration into inflammatory sites is generally preceded by neutrophils. We show here that neutrophils may support this process by activation of CCL15, a human chemokine circulating in blood plasma. Neutrophils were found to release CCL15 proteolytic activity in the course of hemofiltration of blood from renal insufficiency patients. Processing of CCL15 immunoreactivity (IR) in the pericellular space is suggested by a lack of proteolytic activity in blood and blood filtrate, but a shift of the retention time (t_R) of CCL15-IR, detected by chromatographic separation of CCL15-IR in blood and hemofiltrate. CCL15 molecules with N-terminal deletions of 23 (23) and 26 (26) aa were identified as main proteolytic products in hemofiltrate. Neutrophil cathepsin G was identified as the principal protease to produce 23 and 26 CCL15. Also, elastase displays CCL15 proteolytic activity and produces a 21 isoform. Compared with full-length CCL15, 23 and 26 isoforms displayed a significantly increased potency to induce calcium fluxes and chemotactic activity on monocytes and to induce adhesiveness of mononuclear cells to fibronectin. Thus, our findings indicate that activation of monocytes by neutrophils is at least in part induced by quantum proteolytic processing of circulating or endothelium-bound CCL15 by neutrophil cathepsin G.

This article has been cited by other articles:

				L. Tausch, A. Henkel, U. Siemoneit, D. Poeckel, N. Kather, L. Franke, B. Hofmann, G. Schneider, C. Angioni, G. Geisslinger, et al. Identification of Human Cathepsin G As a Functional Target of Boswellic Acids from the Anti-Inflammatory Remedy Frankincense J. Immunol., September 1, 2009; 183(5): 3433 - 3442. [Abstract] [Full Text] [PDF]

				D. Sarker, A. H.M. Reid, T. A. Yap, and J. S. de Bono Targeting the PI3K/AKT Pathway for the Treatment of Prostate Cancer Clin. Cancer Res., August 1, 2009; 15(15): 4799 - 4805. [Abstract] [Full Text] [PDF]

				A. Guillabert, V. Wittamer, B. Bondue, V. Godot, V. Imbault, M. Parmentier, and D. Communi Role of neutrophil proteinase 3 and mast cell chymase in chemerin proteolytic regulation J. Leukoc. Biol., December 1, 2008; 84(6): 1530 - 1538. [Abstract] [Full Text] [PDF]

				H. Roca, Z. Varsos, and K. J. Pienta CCL2 Protects Prostate Cancer PC3 Cells from Autophagic Death via Phosphatidylinositol 3-Kinase/AKT-dependent Survivin Up-regulation J. Biol. Chem., September 5, 2008; 283(36): 25057 - 25073. [Abstract] [Full Text] [PDF]

				N. Shimoda, N. Fukazawa, K. Nonomura, and R. L. Fairchild Cathepsin G Is Required for Sustained Inflammation and Tissue Injury after Reperfusion of Ischemic Kidneys Am. J. Pathol., March 1, 2007; 170(3): 930 - 940. [Abstract] [Full Text] [PDF]