| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Article |
From the Department of Medicine and Hypertension,*
Division of Nephrology and Hypertension, and the Department of
Pathology and Laboratory Medicine,
University
of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and the
Department of Nephrology,
Lund University,
Lund, Sweden
The important issue addressed by the studies presented here is the mechanism of neutrophil-mediated damage to endothelial and epithelial cells during inflammation. Binding of neutrophil-released granule proteins to endothelial cells may be involved in vascular damage in patients with inflammatory vascular diseases. We have determined whether granule proteins proteinase 3(PR3) and/or myeloperoxidase (MPO) are internalized into endothelial cells, as examined by UV light, confocal, and electron microscopy. Coincident induction of apoptosis and/or the generation of intracellular oxidants were monitored. The results indicate that human endothelial cells (human umbilical vein endothelial cells, human umbilical arterial endothelial cells, human lung microvascular endothelial cells) internalize both PR3 and MPO, which are detected on the cell surface, in the cytoplasm, and possibly nuclear. Epithelial cells (small airway epithelial cells) internalized MPO but not PR3, implying that the mechanism of PR3 internalization may be cell-type specific and different from that of MPO. Internalization of PR3, but not MPO, correlated with activation of apoptosis. Internalization of MPO correlated with an increase in intracellular oxidant radicals. The requirement for the proteolytic activity of PR3 for the induction of apoptosis was examined by generating PR3-truncated fragments that did not contain the components of the catalytic triad. An apoptotic function was localized to the C-terminal portion of PR3. These studies reveal novel mechanisms by which the neutrophil granule proteins PR3 and MPO contribute to tissue injury at sites of inflammation.
This article has been cited by other articles:
 |
|
 |
|
  A. Haegens, J. H. J. Vernooy, P. Heeringa, B. T. Mossman, and E. F. M. Wouters Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents Eur. Respir. J., February 1, 2008; 31(2): 252 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Astern, W. F. Pendergraft III, R. J. Falk, J. C. Jennette, A. H. Schmaier, F. Mahdi, and G. A. Preston Myeloperoxidase Interacts with Endothelial Cell-Surface Cytokeratin 1 and Modulates Bradykinin Production by the Plasma Kallikrein-Kinin System Am. J. Pathol., July 1, 2007; 171(1): 349 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C A Dinarello and S-H Kim IL-32, a novel cytokine with a possible role in disease Ann Rheum Dis, November 1, 2006; 65(suppl_3): iii61 - iii64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-S. Sheen, C.-Y. Chu, and H.-S. Yu Antineutrophil cytoplasmic antibody-positive cutaneous leukocytoclastic vasculitis associated with propylthiouracil therapy. Arch Dermatol, July 1, 2006; 142(7): 879 - 880. [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Morgan, L. Harper, J. Williams, and C. Savage Anti-Neutrophil Cytoplasm-Associated Glomerulonephritis J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1224 - 1234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Jennette, H. Xiao, and R. J. Falk Pathogenesis of Vascular Inflammation by Anti-Neutrophil Cytoplasmic Antibodies J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1235 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Novick, M. Rubinstein, T. Azam, A. Rabinkov, C. A. Dinarello, and S.-H. Kim Proteinase 3 is an IL-32 binding protein PNAS, February 28, 2006; 103(9): 3316 - 3321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Korkmaz, S. Attucci, T. Moreau, E. Godat, L. Juliano, and F. Gauthier Design and Use of Highly Specific Substrates of Neutrophil Elastase and Proteinase 3 Am. J. Respir. Cell Mol. Biol., June 1, 2004; 30(6): 801 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhang, J. Yang, J. D. Jacobs, and L. K. Jennings Interaction of myeloperoxidase with vascular NAD(P)H oxidase-derived reactive oxygen species in vasculature: implications for vascular diseases Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2563 - H2572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Sen and D. A Isenberg Antineutrophil cytoplasmic autoantibodies in systemic lupus erythematosus Lupus, September 1, 2003; 12(9): 651 - 658. [Abstract] [PDF]
|
|
|
|
|
|
G. A. Preston, C. S. Zarella, W. F. Pendergraft III, E. H. Rudolph, J. J. Yang, S. B. Sekura, J. C. Jennette, and R. J. Falk Novel Effects of Neutrophil-Derived Proteinase 3 and Elastase on the Vascular Endothelium Involve In Vivo Cleavage of NF-{kappa}B and Proapoptotic Changes in JNK, ERK, and p38 MAPK Signaling Pathways J. Am. Soc. Nephrol., December 1, 2002; 13(12): 2840 - 2849. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
