scholarly journals The pharmacophore of the human C5a anaphylatoxin

1994 ◽  
Vol 3 (8) ◽  
pp. 1159-1168 ◽  
Author(s):  
Matthew J. Toth ◽  
Leslie Huwyler ◽  
William C. Boyar ◽  
Albert F. Braunwalder ◽  
Donna Yarwood ◽  
...  
Keyword(s):  
C5a Anaphylatoxin

scholarly journals Characterization of a Receptor for C5a Anaphylatoxin on Human Eosinophils

1989 ◽  
Vol 264 (3) ◽  
pp. 1760-1766
Author(s):  
N P Gerard ◽  
M K Hodges ◽  
J M Drazen ◽  
P F Weller ◽  
C Gerard
Keyword(s):  
C5a Anaphylatoxin

scholarly journals cDNA Cloning and Characterization of Rat C5a Anaphylatoxin Receptor

1997 ◽  
Vol 41 (7) ◽  
pp. 575-580 ◽  
Author(s):  
Hiroyasu Akatsu ◽  
Takashi Miwa ◽  
Chikai Sakurada ◽  
Yoshihiro Fukuoka ◽  
Julia A. Ember ◽  
...  
Keyword(s):  
Cdna Cloning ◽  
C5a Anaphylatoxin

Cytokines and chemokines triggered by Chikungunya virus infection in human patients during the very early acute phase

2019 ◽  
Vol 113 (11) ◽  
pp. 730-733 ◽  
Author(s):  
Ithallo S B Tanabe ◽  
Elane C Santos ◽  
Eloiza L L Tanabe ◽  
Stephannie J M Souza ◽  
Fabio E F Santos ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Phase ◽  
Chikungunya Virus ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Interferon Α ◽  
Monocyte Chemoattractant Protein 1 ◽  
Illness Onset ◽  
Ifn Γ ◽  
C5a Anaphylatoxin

Abstract Background The immune response against the Chikungunya virus (CHIKV) during the very early acute phase is not fully elucidated. Therefore we explored the cytokine and chemokine profile triggered by CHIKV in infected patients. Methods Cytokines, chemokines and C5a anaphylatoxin were analysed in serum from CHIKV-infected patients during the viraemic phase (mean 2.97±1.27 d after illness onset) compared with a healthy group. Results CHIKV-infected patients had a significant increase of interferon-α (IFN-α), interleukin-6 (IL-6), interleukin-8 (CXCL8/IL-8), interleukin-10 (IL-10), interferon-γ (IFN-γ), monokine induced by interferon-γ (CXCL9/MIG), monocyte chemoattractant protein-1 (CCL2/MCP-1), interferon-γ-induced protein-10 (CXCL10/IP-10) and complement C5a anaphylatoxin. Conclusions The very early acute immune response triggered against CHIKV leads to an increase in pro-inflammatory immune mediators such as IFN-γ and its induced chemokines, and a high level of C5a anaphylatoxin as a result of complement activation.

Responses of isolated pulmonary arteries to the C5a anaphylatoxin

1990 ◽  
Vol 259 (5) ◽  
pp. H1325-H1329 ◽  
Author(s):  
R. E. Crowell ◽  
D. E. Van Epps ◽  
W. P. Reed
Keyword(s):  
Pulmonary Arteries ◽  
H1 Receptor ◽  
Experimental Conditions ◽  
Resting Tension ◽  
Several Variables ◽  
Muscle Tissues ◽  
Anaphylatoxin C5a ◽  
Different Response ◽  
C5a Anaphylatoxin ◽  
H1 Receptor Antagonist

The anaphylatoxin C5a possesses spasmogenic activity in smooth muscle tissues. In this study, we examined the effect of C5a on isolated rabbit pulmonary artery (PA) ring segments under a variety of experimental conditions. C5a (1-100 nM) caused transient constriction of PA at resting tension. C5a-induced PA constriction was not affected by the histamine H1-receptor antagonist pyrilamine (1 microM) but was significantly decreased by the cyclooxygenase inhibitor indomethacin (1 microM). Disruption of the endothelial layer of the vessel had no effect on C5a activity in resting PA. PA, which had been preconstricted with norepinephrine (5 microM), exhibited a different response to C5a than PA at resting tension, however. C5a (1-10 nM) induced a biphasic response in preconstricted PA, initially causing further constriction followed by a greater degree of relaxation resulting in an overall decrease in PA tension. All responses of preconstricted PA to C5a were completely eliminated by indomethacin and significantly depressed by endothelial disruption. These data indicate that C5a interacts directly with isolated rabbit PA, but the nature of the PA response to this peptide depends on several variables including the presence or absence of active PA tension and cyclooxygenase metabolites, and the presence of intact endothelium.

scholarly journals C3 Opsonization of Anthrax Bacterium and Peptidoglycan Supports Recognition and Activation of Neutrophils

2020 ◽  
Vol 8 (7) ◽  
pp. 1039
Author(s):  
Narcis I. Popescu ◽  
Ravi S. Keshari ◽  
Jackie Cochran ◽  
K. Mark Coggeshall ◽  
Florea Lupu
Keyword(s):  
Complement C3 ◽  
Immune Recognition ◽  
Complement Receptors ◽  
Molecular Pattern ◽  
Lower Extent ◽  
Independent Mechanism ◽  
Neutrophil Degranulation ◽  
Particle Ingestion ◽  
C5a Anaphylatoxin

Neutrophils are the most abundant innate cell population and a key immune player against invading pathogens. Neutrophils can kill both bacterium and spores of Bacillus anthracis, the causative anthrax pathogen. Unlike interactions with professional phagocytes, the molecular recognition of anthrax by neutrophils is largely unknown. In this study, we investigated the role of complement C3 deposition on anthrax particles for neutrophil recognition of bacterium and/or its cell wall peptidoglycan, an abundant pathogen-associated molecular pattern that supports anthrax sepsis. C3 opsonization and recognition by complement receptors accounted for 70–80% of the affinity interactions between neutrophils and anthrax particles at subphysiologic temperatures. In contrast, C3 supported up to 50% of the anthrax particle ingestion under thermophysiologic conditions. Opsonin-dependent low affinity interactions and, to a lower extent, opsonin-independent mechanisms, provide alternative entry routes. Similarly, C3 supported 58% of peptidoglycan-induced degranulation and, to a lower extent, 23% of bacterium-induced degranulation. Interestingly, an opsonin independent mechanism mediated by complement C5, likely through C5a anaphylatoxin, primes azurophilic granules in response to anthrax particles. Overall, we show that C3 deposition supports anthrax recognition by neutrophils but is dispensable for pathogen ingestion and neutrophil degranulation, highlighting immune recognition redundancies that minimize the risk of pathogen evasion.

Complement activation-related cardiac anaphylaxis in pigs: role of C5a anaphylatoxin and adenosine in liposome-induced abnormalities in ECG and heart function

2006 ◽  
Vol 290 (3) ◽  
pp. H1050-H1058 ◽  
Author(s):  
János Szebeni ◽  
Lajos Baranyi ◽  
Sándor Sávay ◽  
Michael Bodó ◽  
János Milosevits ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Heart Function ◽  
Cardiac Anaphylaxis ◽  
Cardiac Abnormalities ◽  
Life Threatening ◽  
Amplifying Effect ◽  
C5a Anaphylatoxin

Cardiac anaphylaxis is a severe, life-threatening manifestation of acute hypersensitivity reactions to allergens and drugs. Earlier studies highlighted an amplifying effect of locally applied C5a on the process; however, the role of systemic complement (C) activation with C5a liberation in blood has not been explored to date. In the present study, we used the porcine liposome-induced cardiopulmonary distress model for 1) characterizing and quantifying peripheral C activation-related cardiac dysfunction; 2) exploring the role of C5a in cardiac abnormalities and therapeutic potential of C blockage by soluble C receptor type 1 (sCR1) and an anti-C5a antibody (GS1); and 3) elucidating the role of adenosine and adenosine receptors in paradoxical bradycardia, one of the symptoms observed in this model. Pigs were injected intravenously with different liposomes [Doxil and multilamellar vesicles (MLV)], zymosan, recombinant human (rhu) C5a, and adenosine, and the ensuing hemodynamic and cardiac changes (hypotension, tachy- or bradycardia, arrhythmias, ST-T changes, ventricular fibrillation, and arrest) were quantified by ranking on an arbitrary scale [cardiac abnormality score (CAS)]. There was significant correlation between CAS and C5a production by liposomes in vitro, and the liposome-induced cardiac abnormalities were partially or fully reproduced with zymosan, rhuC5a, adenosine, and the selective adenosine A1 receptor agonist cyclopentyl-adenosine. The use of C nonactivator liposomes or pretreatment of pigs with sCR1 or GS1 attenuated the abnormalities. The selective A1 blocker cyclopentyl-xanthine inhibited bradycardia without influencing hypotension, whereas the A2 blocker 4-(2-{7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino}ethyl)phenol (ZM-24135) had no such effect. These data suggest that 1) systemic C activation can underlie cardiac anaphylaxis, 2) C5a plays a causal role in the reaction, 3) adenosine action via A1 receptors may explain paradoxical bradycardia, and 4) inhibition of C5a formation or action or of A1-receptor function may alleviate the acute cardiotoxicity of liposomal drugs and other intravenous agents that activate C.

Sign in / Sign up

Export Citation Format

Share Document