|
|
Blood, 1 February 2005, Vol. 105, No. 3, pp. 1036-1043.
Prepublished online as a Blood First Edition Paper on September 21, 2004; DOI 10.1182/blood-2004-01-0166.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Angiostatin is a novel anti-inflammatory factor by inhibiting leukocyte recruitment
Triantafyllos Chavakis,
Athanasios Athanasopoulos,
Joong-Sup Rhee,
Valeria Orlova,
Thomas Schmidt-Wöll,
Angelika Bierhaus,
Andreas E. May,
Ilhan Celik,
Peter P. Nawroth, and
Klaus T. Preissner
From the Department of Internal Medicine I, Universität, Heidelberg, Germany; the Institute for Biochemistry, Justus-Liebig-Universität, Giessen, Germany; the Deutsches Herzzentrum, Technische Universität, München, Germany; and the Institute of Theoretical Surgery, Philipps-Universität, Marburg, Germany.
Angiogenesis and inflammation are closely related biologic processes in wound healing and the responses to vascular injury as well as in cardiovascular diseases; however, the molecular connections are poorly defined. In particular, it is yet unclear whether endogenous factors can regulate both angiogenesis and inflammation. Here, we show that the endogenous angiogenesis inhibitor, angiostatin (containing kringle domains 1-4 of plasminogen), serves an anti-inflammatory role, since the kringles 1-3 and its kringle 4 directly interact with leukocyte  1- and 2-integrins, respectively. In particular, a specific interaction between kringle 4 and  M2-integrin (Mac-1) but not leukocyte function antigen 1 (LFA-1) was identified. Angiostatin thereby inhibited 1- and 2-integrin–mediated adhesion of leukocytes to extracellular matrix proteins and the endothelium as well as their transmigration through the endothelium in vitro. Moreover, angiostatin blocked the peritonitis-induced neutrophil emigration in vivo. In addition, through its interaction with Mac-1, angiostatin reduced activation of the proinflammatory transcription factor nuclear factor  B (NFB), as well as the NFB-related expression of tissue factor, a potent initiator of hemostasis following vascular injury. Finally, angiostatin forms were generated in vivo following skin injury/inflammation and were detectable during the following entire period of wound healing peaking at the terminal phase of the healing process. Taken together, over and above inhibition of neovascularization, angiostatin was identified as an antiadhesive/anti-inflammatory substance. These observations could provide the basis for new therapeutic applications of angiostatin to target chronic inflammatory processes in different pathologic situations.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Popovic, Y. Laumonnier, L. Burysek, T. Syrovets, and T. Simmet
Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration
J. Leukoc. Biol.,
July 1, 2008;
84(1):
215 - 223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Shen, Z. F. Yang, Y. Gao, J. C. Li, H. X. Chen, C. C. Liu, R. T.P. Poon, S. T. Fan, J. M. Luk, K. H. Sze, et al.
The Kringle 1 Domain of Hepatocyte Growth Factor Has Antiangiogenic and Antitumor Cell Effects on Hepatocellular Carcinoma
Cancer Res.,
January 15, 2008;
68(2):
404 - 414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. U. Eisenhardt, M. Schwarz, N. Schallner, J. Soosairajah, N. Bassler, D. Huang, C. Bode, and K. Peter
Generation of activation-specific human anti-{alpha}M{beta}2 single-chain antibodies as potential diagnostic tools and therapeutic agents
Blood,
April 15, 2007;
109(8):
3521 - 3528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Perri, D. Martineau, M. Francois, L. Lejeune, L. Bisson, Y. Durocher, and J. Galipeau
Plasminogen Kringle 5 blocks tumor progression by antiangiogenic and proinflammatory pathways
Mol. Cancer Ther.,
February 1, 2007;
6(2):
441 - 449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ohnishi, K. Kakimoto, K. Bandow, C. J. Lowenstein, Y. Daikuhara, and T. Matsuguchi
Mature Hepatocyte Growth Factor/Scatter Factor on the Surface of Human Granulocytes Is Released by a Mechanism Involving Activated Factor Xa.
J. Immunol.,
June 1, 2006;
176(11):
6945 - 6953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. Athanasopoulos, M. Economopoulou, V. V. Orlova, A. Sobke, D. Schneider, H. Weber, H. G. Augustin, S. A. Eming, U. Schubert, T. Linn, et al.
The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms
Blood,
April 1, 2006;
107(7):
2720 - 2727.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
