| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Institut National de la Santé et de la Recherche Médicale Unité 507, Université René Descartes, Paris 5, Hôpital Necker, Paris, France
In the present study, we provide evidence that procaspase-3 is a novel target of proteinase 3 (PR3) but not of human neutrophil elastase (HNE). Human mast cell clone 1 (HMC1) and rat basophilic leukemia (RBL) mast cell lines were transfected with PR3 or the inactive mutated PR3 (PR3S203A) or HNE cDNA. In both RBL/PR3 and HMC1/PR3, a constitutive activity of caspase-3 was measured with DEVD substrate, due to the direct processing of procaspase-3 by PR3. No caspase-3 activation was observed in cells transfected with the inactive PR3 mutant or HNE. Despite the high caspase-3 activity in RBL/PR3, no apoptosis was detected as demonstrated by an absence of 1) phosphatidylserine externalization, 2) mitochondria cytochrome c release, 3) upstream caspase-8 or caspase-9 activation, or 4) DNA fragmentation. In vitro, purified PR3 cleaved procaspase-3 into an active 22-kDa fragment. In neutrophils, the 22-kDa caspase-3 activation fragment was present only in resting neutrophils but was absent after apoptosis. The 22 kDa fragment was specific of myeloid cells because it was absent from resting lymphocytes. This 22-kDa fragment was not present when neutrophils were treated with pefabloc, an inhibitor of serine proteinase. Like in HMC1/PR3, the 22-kDa caspase-3 fragment was restricted to the plasma membrane compartment. Double immunofluorescence labeling after streptolysin-O permeabilization further showed that PR3 and procaspase-3 could colocalize in an extragranular compartment. In conclusion, our results strongly suggest that compartmentalized PR3-induced caspase-3 activation might play specific functions in neutrophil survival.
This article has been cited by other articles:
|
|
 |
|
  C. Kantari, M. Pederzoli-Ribeil, O. Amir-Moazami, V. Gausson-Dorey, I. C. Moura, M.-C. Lecomte, M. Benhamou, and V. Witko-Sarsat Proteinase 3, the Wegener autoantigen, is externalized during neutrophil apoptosis: evidence for a functional association with phospholipid scramblase 1 and interference with macrophage phagocytosis Blood, December 1, 2007; 110(12): 4086 - 4095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Gibb, W. Boston-Howes, Z. S. Lavina, S. Gustincich, R. H. Brown Jr., P. Pasinelli, and D. Trotti A Caspase-3-cleaved Fragment of the Glial Glutamate Transporter EAAT2 Is Sumoylated and Targeted to Promyelocytic Leukemia Nuclear Bodies in Mutant SOD1-linked Amyotrophic Lateral Sclerosis J. Biol. Chem., November 2, 2007; 282(44): 32480 - 32490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Vong, F. D'Acquisto, M. Pederzoli-Ribeil, L. Lavagno, R. J. Flower, V. Witko-Sarsat, and M. Perretti Annexin 1 Cleavage in Activated Neutrophils: A PIVOTAL ROLE FOR PROTEINASE 3 J. Biol. Chem., October 12, 2007; 282(41): 29998 - 30004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huelsenbeck, S. Dreger, R. Gerhard, H. Barth, I. Just, and H. Genth Difference in the Cytotoxic Effects of Toxin B from Clostridium difficile Strain VPI 10463 and Toxin B from Variant Clostridium difficile Strain 1470 Infect. Immun., February 1, 2007; 75(2): 801 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bauer, M. Abdgawad, L. Gunnarsson, M. Segelmark, H. Tapper, and T. Hellmark Proteinase 3 and CD177 are expressed on the plasma membrane of the same subset of neutrophils J. Leukoc. Biol., February 1, 2007; 81(2): 458 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dublet, A. Ruello, M. Pederzoli, E. Hajjar, M. Courbebaisse, S. Canteloup, N. Reuter, and V. Witko-Sarsat Cleavage of p21/WAF1/CIP1 by Proteinase 3 Modulates Differentiation of a Monocytic Cell Line: MOLECULAR ANALYSIS OF THE CLEAVAGE SITE J. Biol. Chem., August 26, 2005; 280(34): 30242 - 30253. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
