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Blood, 15 January 2008, Vol. 111, No. 2, pp. 732-740. Prepublished online as a Blood First Edition Paper on October 4, 2007; DOI 10.1182/blood-2007-05-089821. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-089821v1 111/2/732    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kimura, Y. Articles by Song, W.-C. Search for Related Content PubMed PubMed Citation Articles by Kimura, Y. Articles by Song, W.-C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement Yuko Kimura1, Takashi Miwa1, Lin Zhou1, and Wen-Chao Song1 1 Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia Properdin is a positive regulator of alternative pathway (AP) complement. The current understanding of properdin function is that it facilitates AP complement activation by stabilizing the C3 convertase C3bBb. Properdin-deficient patients are susceptible to lethal meningococcal infection, but the mechanism of this selective predisposition is not fully understood. By gene targeting in the mouse, we show here that properdin is essential for AP complement activation induced by bacterial lipopolysacharride (LPS) and lipooligosacharride (LOS) and other, but not all, AP complement activators. LPS- and LOS-induced AP complement activation was abolished in properdin–/– mouse serum, and properdin–/– mice were unable to clear Crry-deficient erythrocytes, which are known to be susceptible to AP complement–mediated extravascular hemolysis. In contrast, zymosan- and cobra venom factor–induced AP complement activation, and classical pathwaytriggered AP complement amplification were only partially or minimally affected in properdin–/– mice. We further show that the ability of human properdin to restore LPS-dependent AP complement activity in properdin–/– mouse serum correlated with the human properdin-binding affinity of the LPS. These results reveal a novel role of properdin in AP complement initiation and have implications for understanding the selective predisposition of properdin-deficient patients to meningococcal infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. D. Ivanovska, P. A. Dimitrova, J. C. Luckett, R. El-Rachkidy Lonnen, W. J. Schwaeble, and C. M. Stover Properdin Deficiency in Murine Models of Nonseptic Shock J. Immunol., May 15, 2008; 180(10): 6962 - 6969. [Abstract] [Full Text] [PDF]

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