HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huber-Lang, M. Articles by Ward, P. A. Search for Related Content PubMed PubMed Citation Articles by Huber-Lang, M. Articles by Ward, P. A.

Changes in the Novel Orphan, C5a Receptor (C5L2), during Experimental Sepsis and Sepsis in Humans¹

Markus Huber-Lang^2,*, J. Vidya Sarma^2,, Daniel Rittirsch^2,*, Heike Schreiber^*, Manfred Weiss, Michael Flierl^*, Ellen Younkin, Marion Schneider, Heidemarie Suger-Wiedeck, Florian Gebhard^*, Shannon D. McClintock, Thomas Neff, Firas Zetoune, Uwe Bruckner^*, Ren-Feng Guo, Peter N. Monk and Peter A. Ward^3,

Departments of ^* Traumatology, Hand and Reconstructive Surgery, and Anesthesiology, University of Ulm Medical School, Ulm, Germany; Department of Neurology, University of Sheffield Medical School, Sheffield, United Kingdom; and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109

Sepsis is associated with extensive complement activation, compromising innate immune defenses, especially in neutrophils (PMN). Recently, a second C5a receptor (C5L2) was detected on PMN without evidence of intracellular signaling. The current study was designed to determine changes in C5L2 in blood PMN during sepsis. In vitro exposure of PMN to C5a, but not to fMLP, led to reduced content of C5L2. Following cecal ligation and puncture-induced sepsis in rats, PMN demonstrated a time-dependent decrease in C5L2. In vivo blockade of C5a during experimental sepsis resulted in preservation of C5L2. Similarly, PMN from patients with progressive sepsis showed significantly reduced C5L2 expression (n = 26), which was virtually abolished in patients who developed multiorgan failure (n = 10). In contrast, sepsis survivors exhibited retention of C5L2 (n = 12/13). The data suggest that C5L2 on PMN diminishes during sepsis due to systemic generation of C5a, which is associated with a poor prognosis.

This article has been cited by other articles:

				T. M. Woodruff, K. J. Costantini, J. W. Crane, J. D. Atkin, P. N. Monk, S. M. Taylor, and P. G. Noakes The Complement Factor C5a Contributes to Pathology in a Rat Model of Amyotrophic Lateral Sclerosis J. Immunol., December 15, 2008; 181(12): 8727 - 8734. [Abstract] [Full Text] [PDF]

				P. A. Ward Role of the complement in experimental sepsis J. Leukoc. Biol., March 1, 2008; 83(3): 467 - 470. [Abstract] [Full Text] [PDF]

				D. Rittirsch, L. M. Hoesel, and P. A. Ward The disconnect between animal models of sepsis and human sepsis J. Leukoc. Biol., January 1, 2007; 81(1): 137 - 143. [Abstract] [Full Text] [PDF]

				K. Johswich, M. Martin, J. Thalmann, C. Rheinheimer, P. N. Monk, and A. Klos Ligand Specificity of the Anaphylatoxin C5L2 Receptor and Its Regulation on Myeloid and Epithelial Cell Lines J. Biol. Chem., December 22, 2006; 281(51): 39088 - 39095. [Abstract] [Full Text] [PDF]

				T. M. Woodruff, J. W. Crane, L. M. Proctor, K. M. Buller, A. B. Shek, K. de Vos, S. Pollitt, H. M. Williams, I. A. Shiels, P. N. Monk, et al. Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration FASEB J, July 1, 2006; 20(9): 1407 - 1417. [Abstract] [Full Text] [PDF]