| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Section of General Pathology, Department of Pathology, University of Verona, Verona, Italy;
Molecular Biology Laboratory and Tumor Progression Section, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; and
Section of General Pathology, Department of Biotechnology, University of Brescia, Brescia, Italy
The contribution of polymorphonuclear neutrophils (PMN) to host defense and natural immunity extends well beyond their traditional role as professional phagocytes. In this study, we demonstrate that upon stimulation with proinflammatory stimuli, human PMN release enzymatic activities that, in vitro, generate bioactive angiostatin fragments from purified plasminogen. We also provide evidence that these angiostatin-like fragments, comprising kringle domain 1 to kringle domain 3 (kringle 1–3) of plasminogen, are generated as a byproduct of the selective proteolytic activity of neutrophil-secreted elastase. Remarkably, affinity-purified angiostatin kringle 1–3 fragments generated by neutrophils inhibited basic fibroblast growth factor plus vascular endothelial growth factor-induced endothelial cell proliferation in vitro, and both vascular endothelial growth factor-induced angiogenesis in the matrigel plug assay and fibroblast growth factor-induced angiogenesis in the chick embryo chorioallantoic membrane assay, in vivo. These results represent the first demonstration that biologically active angiostatin-like fragments can be generated by inflammatory human neutrophils. Because angiostatin is a potent inhibitor of angiogenesis, tumor growth, and metastasis, the data suggest that activated PMN not only act as potent effectors of inflammation, but might also play a critical role in the inhibition of angiogenesis in inflammatory diseases and tumors, by generation of a potent anti-angiogenic molecule.
This article has been cited by other articles:
|
|
 |
|
  D. J. Bautz, G. A. Preston, S. Lionaki, P. Hewins, A. S. Wolberg, J. J. Yang, S. L. Hogan, H. Chin, S. Moll, J. C. Jennette, et al. Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2421 - 2429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Pluskota, D. A. Soloviev, D. Szpak, C. Weber, and E. F. Plow Neutrophil Apoptosis: Selective Regulation by Different Ligands of Integrin {alpha}M{beta}2 J. Immunol., September 1, 2008; 181(5): 3609 - 3619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Deban, C. Correale, S. Vetrano, A. Malesci, and S. Danese Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades Am. J. Pathol., June 1, 2008; 172(6): 1457 - 1466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. M. Dirkx, M. G. A. oude Egbrink, J. Wagstaff, and A. W. Griffioen Monocyte/macrophage infiltration in tumors: modulators of angiogenesis J. Leukoc. Biol., December 1, 2006; 80(6): 1183 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nozawa, C. Chiu, and D. Hanahan Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis PNAS, August 15, 2006; 103(33): 12493 - 12498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Cassatella On the production of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2L) by human neutrophils J. Leukoc. Biol., June 1, 2006; 79(6): 1140 - 1149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lu, W. Ouyang, and C. Huang Inflammation, a Key Event in Cancer Development Mol. Cancer Res., April 1, 2006; 4(4): 221 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Economopoulou, K. Bdeir, D. B. Cines, F. Fogt, Y. Bdeir, J. Lubkowski, W. Lu, K. T. Preissner, H.-P. Hammes, and T. Chavakis Inhibition of pathologic retinal neovascularization by {alpha}-defensins Blood, December 1, 2005; 106(12): 3831 - 3838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Leksa, S. Godar, H. B. Schiller, E. Fuertbauer, A. Muhammad, K. Slezakova, V. Horejsi, P. Steinlein, U. H. Weidle, B. R. Binder, et al. TGF-{beta}-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen J. Cell Sci., October 1, 2005; 118(19): 4577 - 4586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Chavakis, A. Athanasopoulos, J.-S. Rhee, V. Orlova, T. Schmidt-Woll, A. Bierhaus, A. E. May, I. Celik, P. P. Nawroth, and K. T. Preissner Angiostatin is a novel anti-inflammatory factor by inhibiting leukocyte recruitment Blood, February 1, 2005; 105(3): 1036 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Scapini, M. Morini, C. Tecchio, S. Minghelli, E. Di Carlo, E. Tanghetti, A. Albini, C. Lowell, G. Berton, D. M. Noonan, et al. CXCL1/Macrophage Inflammatory Protein-2-Induced Angiogenesis In Vivo Is Mediated by Neutrophil-Derived Vascular Endothelial Growth Factor-A J. Immunol., April 15, 2004; 172(8): 5034 - 5040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Perchick and H. N. Jabbour Cyclooxygenase-2 Overexpression Inhibits Cathepsin D-Mediated Cleavage of Plasminogen to the Potent Antiangiogenic Factor Angiostatin Endocrinology, December 1, 2003; 144(12): 5322 - 5328. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
