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Title	Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection
Author	Atkinson, Carl Song, Hongbin Lu, Bo Qiao, Fei Burns, Tara A. Holers, V. Michael Tsokos, George C. Tomlinson, Stephen
Contributor(s)	Journal of Clinical Investigation (Publisher)
Date	2005-09
Affiliation/College	College of Graduate Studies
Department	Microbiology and Immunology
Subject.MeSH	Mice Receptors, Complement 3d Biological Availability Half-Life Complement C3b Complement Activation Peptide Fragments Complement Inactivating Agents Reperfusion Injury Intestines Peritonitis
Collection	MUSC Faculty Journal Articles
Contributing Institution	Waring Historical Library (MUSC)
Rights	Copyright © 2005 The American Society for Clinical Investigation, Inc. For more information contact the Waring Historical Library, Charleston, SC 29425.
Language	English
Type	Text
Format	application/pdf
Media Type	Periodicals
Resource Identifier	fja_2005_0003
Abstract	Previous studies indicate a pivotal role for complement in mediating both local and remote injury following ischemia and reperfusion of the intestine. Here, we report on the use of a mouse model of intestinal ischemia/ reperfusion injury to investigate the strategy of targeting complement inhibition to sites of complement activation by linking an iC3b/C3dg-binding fragment of mouse complement receptor 2 (CR2) to a mouse complement-inhibitory protein, Crry. We show that the novel CR2-Crry fusion protein targets sites of local and remote (lung) complement activation following intestinal ischemia and reperfusion injury and that CR2- Crry requires a 10-fold lower dose than its systemic counterpart, Crry-Ig, to provide equivalent protection from both local and remote injury. CR2-Crry has a significantly shorter serum half-life than Crry-Ig and, unlike Crry-Ig, had no significant effect on serum complement activity at minimum effective therapeutic doses. Furthermore, the minimum effective dose of Crry-Ig significantly enhanced susceptibility to infection in a mouse model of acute septic peritonitis, whereas the effect of CR2-Crry on susceptibility to infection was indistinguishable from that of PBS control. Thus, compared with systemic inhibition, CR2-mediated targeting of a complement inhibitor of activation improved bioavailability, significantly enhanced efficacy, and maintained host resistance to infection.
Bibliographic Citation	Atkinson, C., Song, H., Lu, B., Qiao, F., Burns, T. A., Holers, V. M.,...Tomlinson, S. (2005). Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection, The Journal of Clinical Investigation, 115(9), 2444–2453: https://doi.org/10.1172/JCI25208

Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection

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