In Vivo Pharmacodynamic Method to Assess Complement C5a Receptor Antagonist Efficacy

2021 ◽  
Author(s):  
Cedric S. Cui ◽  
Vinod Kumar ◽  
Declan M. Gorman ◽  
Richard J. Clark ◽  
John D. Lee ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
C5a Receptor ◽  
Complement C5a

Blockade of the Complement C5a Receptor Reduces Incisional Allodynia, Edema, and Cytokine Expression

2006 ◽  
Vol 104 (6) ◽  
pp. 1274-1282 ◽  
Author(s):  
J David Clark ◽  
Yanli Qiao ◽  
Xiangqi Li ◽  
Xiaoyou Shi ◽  
Martin S. Angst ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Complement System ◽  
Messenger Rna ◽  
Receptor Expression ◽  
Daily Injection ◽  
Edema Formation ◽  
C5a Receptor ◽  
Surgical Incisions ◽  
Complement C5a ◽  
The Complement System

Background Activation of the complement system is one component of the inflammatory response. Various components of the complement system participate in killing foreign organisms, recruiting immune cells, enhancing edema, and stimulating cytokine formation. Complement-mediated enhancement of the inflammation surrounding surgical incisions may increase pain. Methods In these studies, the authors used a murine hind paw incisional model to study the role of the complement C5a receptor in supporting incisional inflammation. At baseline and at various time points after incision, they measured the effects of a highly selective C5a receptor antagonist on nociceptive thresholds, edema formation, and cytokine production in the skin surrounding the incision. They also measured changes in C5a receptor expression near the incisions. Results The once-daily injection of the C5a receptor antagonist AcF-[OPdChaWR] reduced mechanical allodynia and edema in the incised hind paw. A multiplexed cytokine assay revealed that 8 of the 18 cytokines examined showed significant increases in skin tissue abundance after incision. Distinct time courses for the patterns of elevation were seen, though some degree of resolution occurred for all cytokines within 96 h. For 7 of these 8 cytokines, the C5a receptor antagonist reduced the enhancement of expression. In addition, the authors found that the C5a receptor messenger RNA level increased 15-fold in the skin surrounding the incisions within 24 h and then slowly declined. Conclusions The tissue directly surrounding incisions in mouse hind paws undergoes large changes in the content of specific cytokines in addition to demonstrating edema and nociceptive sensitization. By blocking the receptor for one component of the complement system, C5a, all of these changes can be reduced. Complement receptor inhibitors may constitute a novel group of compounds useful in reducing the pain and swelling of surgical incisions.

scholarly journals An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction

2005 ◽  
Vol 203 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Andreas D. Niederbichler ◽  
Laszlo M. Hoesel ◽  
Margaret V. Westfall ◽  
Hongwei Gao ◽  
Kyros R. Ipaktchi ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cecal Ligation ◽  
Left Ventricular ◽  
C5a Receptor ◽  
Blocking Antibody ◽  
Cardiomyocyte Contractility ◽  
Complement C5a ◽  
The Complement System

Defective cardiac function during sepsis has been referred to as “cardiomyopathy of sepsis.” It is known that sepsis leads to intensive activation of the complement system. In the current study, cardiac function and cardiomyocyte contractility have been evaluated in rats after cecal ligation and puncture (CLP). Significant reductions in left ventricular pressures occurred in vivo and in cardiomyocyte contractility in vitro. These defects were prevented in CLP rats given blocking antibody to C5a. Both mRNA and protein for the C5a receptor (C5aR) were constitutively expressed on cardiomyocytes; both increased as a function of time after CLP. In vitro addition of recombinant rat C5a induced dramatic contractile dysfunction in both sham and CLP cardiomyocytes, but to a consistently greater degree in cells from CLP animals. These data suggest that CLP induces C5aR on cardiomyocytes and that in vivo generation of C5a causes C5a–C5aR interaction, causing dysfunction of cardiomyocytes, resulting in compromise of cardiac performance.

scholarly journals Recombinant human complement C5a receptor antagonist reduces infarct size after surgical revascularization

2000 ◽  
Vol 120 (2) ◽  
pp. 350-358 ◽  
Author(s):  
Robert D. Riley ◽  
Hiroki Sato ◽  
Zhi-Qing Zhao ◽  
Vinod H. Thourani ◽  
James E. Jordan ◽  
...  
Keyword(s):  
Infarct Size ◽  
Receptor Antagonist ◽  
Human Complement ◽  
Surgical Revascularization ◽  
C5a Receptor ◽  
Complement C5a

A C5a mutant selected from a phage library is a potent C5a-receptor antagonist in vitro and in vivo

1998 ◽  
Vol 35 (6-7) ◽  
pp. 365 ◽  
Author(s):  
T. Heller ◽  
M. Hennecke ◽  
M. Baensch ◽  
F. Boulay ◽  
A. Kola ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Phage Library ◽  
C5a Receptor

Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity

2021 ◽  
Author(s):  
Declan M. Gorman ◽  
Xaria X. Li ◽  
John D. Lee ◽  
Jenny N. Fung ◽  
Cedric S. Cui ◽  
...  
Keyword(s):  
C5a Receptor ◽  
Selective Agonists ◽  
Complement C5a

Inhibition of Inflammation and Fibrosis by a Complement C5a Receptor Antagonist in DOCA-Salt Hypertensive Rats

2011 ◽  
Vol 58 (5) ◽  
pp. 479-486 ◽  
Author(s):  
Abishek Iyer ◽  
Trent M. Woodruff ◽  
Mike C.L. Wu ◽  
Con Stylianou ◽  
Robert C. Reid ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Hypertensive Rats ◽  
C5a Receptor ◽  
Complement C5a

scholarly journals Complement C5a receptor antagonist attenuates placental ischemia‐induced hypertension in rat (1084.7)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Jenna Peterson ◽  
Kathryn Lillegard ◽  
Barbara Elmquist ◽  
Jeffrey Gilbert ◽  
Jean Regal
Keyword(s):  
Receptor Antagonist ◽  
C5a Receptor ◽  
Induced Hypertension ◽  
Complement C5a ◽  
Placental Ischemia

scholarly journals Synthesis, in vitro and in vivo evaluation of 11C-O-methylated arylpiperazines as potential serotonin 1A (5-HT1A) receptor antagonist radiotracers

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Vidya Narayanaswami ◽  
Junchao Tong ◽  
Ferdinando Fiorino ◽  
Beatrice Severino ◽  
Rosa Sparaco ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
In Vivo Evaluation
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