Functional roles for C5a receptors in sepsis

被引：316

作者：

Rittirsch, Daniel ^{[1
]}

Flierl, Michael A. ^{[1
]}

Nadeau, Brian A. ^{[1
]}

Day, Danielle E. ^{[1
]}

Huber-Lang, Markus ^{[2
]}

Mackay, Charles R. ^{[3
]}

Zetoune, Firas S. ^{[1
]}

Gerard, Norma P. ^{[4
,5
]}

Cianflone, Katherine ^{[6
]}

Koehl, Joerg ^{[7
,8
]}

Gerard, Craig ^{[4
]}

Sarma, J. Vidya ^{[1
]}

Award, Peter ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[2] Univ Hosp, Dept Traumatol Hand Plast & Reconstruct Surg, D-89075 Ulm, Germany

[3] St Vincents Hosp, Garvan Inst Med Res, Immunol & Inflammat Dept, Darlinghurst, NSW 2010, Australia

[4] Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat,Pulm Div, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[6] Univ Laval, Hop Laval, Ctr Rech, Ste Foy, PQ G1V 4G5, Canada

[7] Cincinnati Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH 45229 USA

[8] Med Univ Lubeck, Inst Systemat Inflammat Res, D-23538 Lubeck, Germany

来源：

NATURE MEDICINE | 2008年 / 14卷 / 05期

关键词：

D O I：

10.1038/nm1753

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The function of the C5a receptors, C5ar ( encoded by C5ar) and C512 ( encoded by Gpr77), especially of C512, which was originally termed a 'default receptor', remains a controversial topic. Here we investigated the role of each receptor in the setting of cecal ligation and puncture-induced sepsis by using antibody-induced blockade of C5a receptors and knockout mice. In 'mid-grade' sepsis ( 30-40% survival), blockade or absence of either C5ar or C512 greatly improved survival and attenuated the buildup of proinflammatory mediators in plasma. In vivo appearance or in vitro release of high mobility group box 1 protein ( HMGB1) required C512 but not C5ar. In 'high-grade' sepsis ( 100% lethality), the only protective condition was the combined blockade of C512 and C5ar. These data suggest that C5ar and C512 contribute synergistically to the harmful consequences in sepsis and that C512 is required for the release of HMGB1. Thus, contrary to earlier speculation, C512 is a functional receptor rather than merely a default receptor.

引用

页码：551 / 557

页数：7

共 38 条

[1] Pharmacological targeting of anaphylatoxin receptors during the effector phase of allergic asthma suppresses airway hyperresponsiveness and airway inflammation [J].