The Journal of Immunology, Vol 152, Issue 7 3595-3605, Copyright © 1994 by American Association of Immunologists

ARTICLES

Two proteolytic pathways for down-regulation of the barrier molecule CD43 of human neutrophils

E Remold-O'Donnell and D Parent
Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115.

CD43, an anionic rod-like mucin molecule on white blood cells, is thought to provide a barrier that prevents interactions of other surface molecules and acts as negative regulator of cell function. As a correlate, CD43 is expected to be altered or down-regulated when blood cells are functionally activated. This study examines CD43 of blood neutrophils before and after treatment with known activating agents. Flow cytometry indicated that PMA and A23187, and to a much lesser extent, FMLP and IL-8, decrease neutrophil expression of CD43. Two separate mechanisms were identified for CD43 down-regulation. Both are proteolytic processes. PMA-induced down-regulation is a rapid process involving proteolysis at a minimum of two sites, one within the N- terminal distal region recognized by mAbs and the other at a membrane- proximal site. The PMA-induced protease, cd43' ase, is characterized by insensitivity to DFP, TLCK, leupeptin, pepstatin, and 1,10 phenanthroline (< 5 mM). PMA-induced CD43 down-regulation is extensive but never complete, terminating at approximately 10 min after down- regulating 65 to 85% of molecules, and thereby converting neutrophils from dense to sparse CD43 expression. The second CD43 down-regulation mechanism, although likely a regulated event in vivo, occurred slowly in this study in neutrophils incubated without additives; the process is not affected by PMA, involves the action of a DFP-sensitive protease, releases N-terminal mAb-reactive fragments of 52 kDa or 40 kDa and can be mimicked by exogenous neutrophil elastase. The complexity and apparent tight regulation described here for the two down-regulatory mechanisms are consistent with an important role for CD43 in preventing or dampening cell surface interactions of blood neutrophils.

This article has been cited by other articles:

				W. Seo and H. J. Ziltener CD43 processing and nuclear translocation of CD43 cytoplasmic tail are required for cell homeostasis Blood, October 22, 2009; 114(17): 3567 - 3577. [Abstract] [Full Text] [PDF]

				A. Mambole, D. Baruch, P. Nusbaum, S. Bigot, M. Suzuki, P. Lesavre, M. Fukuda, and L. Halbwachs-Mecarelli The Cleavage of Neutrophil Leukosialin (CD43) by Cathepsin G Releases Its Extracellular Domain and Triggers Its Intramembrane Proteolysis by Presenilin/{gamma}-Secretase J. Biol. Chem., August 29, 2008; 283(35): 23627 - 23635. [Abstract] [Full Text] [PDF]

				P. Nusbaum, C. Laine, M. Bouaouina, S. Seveau, E. M. Cramer, J. M. Masse, P. Lesavre, and L. Halbwachs-Mecarelli Distinct Signaling Pathways Are Involved in Leukosialin (CD43) Down-regulation, Membrane Blebbing, and Phospholipid Scrambling during Neutrophil Apoptosis J. Biol. Chem., February 18, 2005; 280(7): 5843 - 5853. [Abstract] [Full Text] [PDF]

				S. Eda, M. Yamanaka, and M. Beppu Carbohydrate-mediated Phagocytic Recognition of Early Apoptotic Cells Undergoing Transient Capping of CD43 Glycoprotein J. Biol. Chem., February 13, 2004; 279(7): 5967 - 5974. [Abstract] [Full Text] [PDF]

				N. Da Silva, A. Bharti, and C. S. Shelley hnRNP-K and Puralpha act together to repress the transcriptional activity of the CD43 gene promoter Blood, November 15, 2002; 100(10): 3536 - 3544. [Abstract] [Full Text] [PDF]

				C. S. Shelley, J. M. Teodoridis, H. Park, O. C. Farokhzad, E. P. Bottinger, and M. A. Arnaout During Differentiation of the Monocytic Cell Line U937, Pur{alpha} Mediates Induction of the CD11c{beta}2 Integrin Gene Promoter J. Immunol., April 15, 2002; 168(8): 3887 - 3893. [Abstract] [Full Text] [PDF]

				O. C. Farokhzad, J. M. Teodoridis, H. Park, M. A. Arnaout, and C. S. Shelley CD43 gene expression is mediated by a nuclear factor which binds pyrimidine-rich single-stranded DNA Nucleic Acids Res., June 1, 2000; 28(11): 2256 - 2267. [Abstract] [Full Text] [PDF]

				S Sabri, M Soler, C Foa, A Pierres, A Benoliel, and P Bongrand Glycocalyx modulation is a physiological means of regulating cell adhesion J. Cell Sci., January 5, 2000; 113(9): 1589 - 1600. [Abstract] [PDF]

				M. Fabbi, J. Geginat, M. Tiso, D. Ramarli, D. Parent, A. Bargellesi, and E. Remold-O'Donnell 8B4/20, A Private CD43 Epitope on Developing Human Thymocytes, Is Involved in Thymocyte Maturation J. Immunol., December 1, 1999; 163(11): 5964 - 5970. [Abstract] [Full Text] [PDF]

				P. Dri, E. Haas, R. Cramer, R. Menegazzi, C. Gasparini, R. Martinelli, P. Scheurich, and P. Patriarca Role of the 75-kDa TNF Receptor in TNF-Induced Activation of Neutrophil Respiratory Burst J. Immunol., January 1, 1999; 162(1): 460 - 466. [Abstract] [Full Text] [PDF]

				R. C. Woodman, B. Johnston, M. J. Hickey, D. Teoh, P. Reinhardt, B. Y. Poon, and P. Kubes The Functional Paradox of CD43 in Leukocyte Recruitment: A Study Using CD43-deficient Mice J. Exp. Med., December 7, 1998; 188(11): 2181 - 2186. [Abstract] [Full Text] [PDF]

				S Seveau, S Lopez, P Lesavre, J Guichard, E. Cramer, and L Halbwachs-Mecarelli Leukosialin (CD43, sialophorin) redistribution in uropods of polarized neutrophils is induced by CD43 cross-linking by antibodies, by colchicine or by chemotactic peptides J. Cell Sci., January 7, 1997; 110(13): 1465 - 1475. [Abstract] [PDF]

				W.-W. Tchou, W. N. Rom, and K.-M. Tchou-Wong Novel Form of p21WAF1/CIP1/SDI1 Protein in Phorbol Ester-induced G2/M Arrest J. Biol. Chem., November 22, 1996; 271(47): 29556 - 29560. [Abstract] [Full Text] [PDF]

				D. Baeckström, K. Zhang, N. Asker, U. Rüetschi, M. Ek, and G. C. Hansson Expression of the Leukocyte-associated Sialoglycoprotein CD43 by a Colon Carcinoma Cell Line J. Biol. Chem., June 9, 1995; 270(23): 13688 - 13692. [Abstract] [Full Text] [PDF]