Mapping the signalling pathways and interactions for the complement C5a receptors using novel methodologies

2014 ◽  
Author(s):  
Daniel Croker
Keyword(s):  
Signalling Pathways ◽  
C5a Receptors ◽  
Complement C5a

scholarly journals Complement C5a receptors in the pituitary gland: expression and function

2008 ◽  
Vol 199 (3) ◽  
pp. 417-424 ◽  
Author(s):  
Karen Francis ◽  
B Mary Lewis ◽  
Peter N Monk ◽  
Jack Ham
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Endocrine System ◽  
Anterior Pituitary Gland ◽  
Signal Molecules ◽  
C5a Receptors ◽  
Dependent Inhibition ◽  
Ic50 Values ◽  
Complement C5a ◽  
And Function

Communication between the immune and endocrine system is important for the control of inflammation that is primarily mediated through the hypothalamic–pituitary–adrenal axis. The innate immune system rapidly responds to pathogens by releasing complement proteins that include the anaphylatoxins C3a and C5a. We previously reported the existence of C3a receptors in the anterior pituitary gland and now describe the presence of C5a receptors in the gland. C5a and its less active derivative (C5adR) can bind to its own receptor and to another receptor called C5L2. Using RT-PCR and immunocytochemistry, C5a receptors and C5L2 were demonstrated in the rat anterior pituitary gland and in several rodent anterior pituitary cell lines. Western blotting analysis showed that C5a stimulated the phosphorylation of MAPK and AKT but not p38; C5adR on the other hand, had no effect on any of the signal molecules investigated. The effects of C5a and C5adR on the secretion of the inflammatory molecule, macrophage migration inhibitory factor (MIF) were investigated by ELISA. Both compounds showed a dose-dependent inhibition of MIF release, 30–40% inhibition at around 35–70 nM agonist with IC50 values of around 20 nM. C5a and C5adR also stimulated ACTH secretion (up to 25%) from AtT-20DV16 cells. These data show that functional C5a receptors (C5a and C5L2) are present in the anterior pituitary gland and they may play a role in dampening down inflammation by inhibiting the release of MIF and stimulating the release of ACTH.

scholarly journals Function, structure and therapeutic potential of complement C5a receptors

2007 ◽  
Vol 152 (4) ◽  
pp. 429-448 ◽  
Author(s):  
P N Monk ◽  
A-M Scola ◽  
P Madala ◽  
D P Fairlie
Keyword(s):  
Therapeutic Potential ◽  
Function Structure ◽  
C5a Receptors ◽  
Complement C5a

C5a, but not C5a‐des Arg, induces upregulation of heteromer formation between complement C5a receptors C5aR and C5L2

2013 ◽  
Vol 91 (10) ◽  
pp. 625-633 ◽  
Author(s):  
Daniel E Croker ◽  
Reena Halai ◽  
David P Fairlie ◽  
Matthew A Cooper
Keyword(s):  
C5a Receptors ◽  
Complement C5a

scholarly journals Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome

2004 ◽  
Vol 113 (4) ◽  
pp. 646-646
Author(s):  
Guillermina Girardi ◽  
Jessica Berman ◽  
Patricia Redecha ◽  
Lynn Spruce ◽  
Joshua M. Thurman ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
C5a Receptors ◽  
Complement C5a

scholarly journals Complement C5a impairs phagosomal maturation in the neutrophil through phosphoproteomic remodelling

2020 ◽  
Author(s):  
Alexander J.T. Wood ◽  
Arlette M. Vassallo ◽  
Marie-Hélène Ruchaud-Sparagano ◽  
Jonathan Scott ◽  
Carmelo Zinnato ◽  
...  
Keyword(s):  
Critical Illness ◽  
Protein Phosphorylation ◽  
Adverse Outcomes ◽  
Proton Channel ◽  
Signalling Pathways ◽  
Phosphatidylinositol 3 Kinase ◽  
Phagosomal Maturation ◽  
Complement C5a ◽  
Neutrophil Dysfunction ◽  
Selective Impairment

AbstractCritical illness is accompanied by the release of large amounts of the anaphylotoxin, C5a. C5a suppresses antimicrobial functions of neutrophils which is associated with adverse outcomes. The signalling pathways that mediate C5a-induced neutrophil dysfunction are incompletely understood. Healthy donor neutrophils exposed to purified C5a demonstrated a prolonged defect (7 hours) in phagocytosis of Staphylococcus aureus. Phosphoproteomic profiling of 2712 phosphoproteins identified persistent C5a signalling and selective impairment of phagosomal protein phosphorylation on exposure to S. aureus. Notable proteins included early endosomal marker ZFYVE16 and V-ATPase proton channel component ATPV1G1. A novel assay of phagosomal acidification demonstrated C5a-induced impairment of phagosomal acidification which was recapitulated in neutrophils from critically ill patients. Examination of the C5a-impaired protein phosphorylation indicated a role for the phosphatidylinositol 3-kinase VPS34 in phagosomal maturation. Inhibition of VPS34 impaired neutrophil phagosomal acidification and killing of S. aureus. This study provides a phosphoproteomic assessment of human neutrophil signalling in response to S. aureus and its disruption by C5a, identifying a defect in phagosomal maturation and new mechanisms of immune failure in critical illness.

scholarly journals Fosbgene products contribute to excitotoxic microglial activation by regulating the expression of complement C5a receptors in microglia

Glia ◽  
2014 ◽  
Vol 62 (8) ◽  
pp. 1284-1298 ◽  
Author(s):  
Hiroko Nomaru ◽  
Kunihiko Sakumi ◽  
Atsuhisa Katogi ◽  
Yoshinori N. Ohnishi ◽  
Kosuke Kajitani ◽  
...  
Keyword(s):  
Microglial Activation ◽  
C5a Receptors ◽  
Complement C5a
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