Published online before print July 15, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0403141v1 74/3/389    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walcheck, B. Articles by Matala, E. Search for Related Content PubMed PubMed Citation Articles by Walcheck, B. Articles by Matala, E.

(Journal of Leukocyte Biology. 2003;74:389-394.)
© 2003 by Society for Leukocyte Biology

ADAM-17-independent shedding of L-selectin

The Center for Immunology and the Departments of Veterinary PathoBiology and Laboratory Medicine and Pathology, University of Minnesota Academic Health Center, University of Minnesota, St. Paul

¹Correspondence: University of Minnesota, 295j AS/VM Bldg., 1988 Fitch Ave., St. Paul, MN 55108. E-mail: walch003{at}umn.edu

L-selectin is expressed by leukocytes and facilitates their adhesion under flow along the walls of blood vessels. As do a variety of membrane proteins, L-selectin undergoes ectodomain shedding. Using approaches that monitor full-length L-selectin in short-term assays, it has been determined that L-selectin shedding is defective in tumor necrosis factor -converting enzyme (ADAM-17)-deficient cells. In this study, we examined the steady-state levels of L-selectin on ADAM-17-deficient cells using a monoclonal antibody to the cytoplasmic region of L-selectin, which allows for the detection of total L-selectin (full-length and the membrane-associated cleavage fragment). We demonstrate that ADAM-17-deficient cells generate a 6-kDa transmembrane fragment of L-selectin. Although inducible L-selectin shedding by phorbol 12-myristate 13-acetate stimulation was not observed by these cells in short-term assays, basal turnover did occur, resulting in the production of soluble L-selectin, as determined by enzyme-linked immunosorbent assay. L-selectin turnover was greatly increased upon ADAM-17 reconstitution. Truncating the juxtamembrane region of L-selectin blocked ADAM-17-independent shedding as did a hydroxymate metalloprotease inhibitor. Together, these findings demonstrate that a metalloprotease activity separate from ADAM-17 can use the cleavage domain of L-selectin. We speculate that separate proteolytic mechanisms of L-selectin shedding may regulate distinct antiadhesive mechanisms, such as inducible shedding for the rapid dissociation of cell–cell interactions and constitutive shedding for the homeostatic maintenance of high serum levels of soluble L-selectin, a potential adhesion buffer.

Key Words: inflammation • adhesion • endoproteolysis

This article has been cited by other articles:

				Y. Wang, A. H. Herrera, Y. Li, K. K. Belani, and B. Walcheck Regulation of Mature ADAM17 by Redox Agents for L-Selectin Shedding J. Immunol., February 15, 2009; 182(4): 2449 - 2457. [Abstract] [Full Text] [PDF]

				I. Ahrens, C. Ellwanger, B. K. Smith, N. Bassler, Y. C. Chen, I. Neudorfer, A. Ludwig, C. Bode, and K. Peter Selenium supplementation induces metalloproteinase-dependent L-selectin shedding from monocytes J. Leukoc. Biol., June 1, 2008; 83(6): 1388 - 1395. [Abstract] [Full Text] [PDF]

				U. Schaff, P. E. Mattila, S. I. Simon, and B. Walcheck Neutrophil adhesion to E-selectin under shear promotes the redistribution and co-clustering of ADAM17 and its proteolytic substrate L-selectin J. Leukoc. Biol., January 1, 2008; 83(1): 99 - 105. [Abstract] [Full Text] [PDF]

				M. Gomez-Gaviro, M. Dominguez-Luis, J. Canchado, J. Calafat, H. Janssen, E. Lara-Pezzi, A. Fourie, A. Tugores, A. Valenzuela-Fernandez, F. Mollinedo, et al. Expression and Regulation of the Metalloproteinase ADAM-8 during Human Neutrophil Pathophysiological Activation and Its Catalytic Activity on L-Selectin Shedding J. Immunol., June 15, 2007; 178(12): 8053 - 8063. [Abstract] [Full Text] [PDF]

				Y. Li, J. Brazzell, A. Herrera, and B. Walcheck ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding Blood, October 1, 2006; 108(7): 2275 - 2279. [Abstract] [Full Text] [PDF]

				S. Sengstake, E.-M. Boneberg, and H. Illges CD21 and CD62L shedding are both inducible via P2X7Rs Int. Immunol., July 1, 2006; 18(7): 1171 - 1178. [Abstract] [Full Text] [PDF]

				P. E. Mattila, C. E. Green, U. Schaff, S. I. Simon, and B. Walcheck Cytoskeletal interactions regulate inducible L-selectin clustering Am J Physiol Cell Physiol, August 1, 2005; 289(2): C323 - C332. [Abstract] [Full Text] [PDF]

				A. Garcia-Touchard, T. D. Henry, G. Sangiorgi, L. G. Spagnoli, A. Mauriello, C. Conover, and R. S. Schwartz Extracellular Proteases in Atherosclerosis and Restenosis Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1119 - 1127. [Abstract] [Full Text] [PDF]

				T. Rabie, A. Strehl, A. Ludwig, and B. Nieswandt Evidence for a Role of ADAM17 (TACE) in the Regulation of Platelet Glycoprotein V J. Biol. Chem., April 15, 2005; 280(15): 14462 - 14468. [Abstract] [Full Text] [PDF]

				W. Bergmeier, C. L. Piffath, G. Cheng, V. S. Dole, Y. Zhang, U. H. von Andrian, and D. D. Wagner Tumor Necrosis Factor-{alpha}-Converting Enzyme (ADAM17) Mediates GPIb{alpha} Shedding From Platelets In Vitro and In Vivo Circ. Res., October 1, 2004; 95(7): 677 - 683. [Abstract] [Full Text] [PDF]