RGD Reference Report - The complement anaphylatoxin C5a induces apoptosis in adrenomedullary cells during experimental sepsis. - Rat Genome Database

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The complement anaphylatoxin C5a induces apoptosis in adrenomedullary cells during experimental sepsis.

Authors: Flierl, MA  Rittirsch, D  Chen, AJ  Nadeau, BA  Day, DE  Sarma, JV  Huber-Lang, MS  Ward, PA 
Citation: Flierl MA, etal., PLoS One. 2008 Jul 2;3(7):e2560.
RGD ID: 5130170
Pubmed: PMID:18648551   (View Abstract at PubMed)
PMCID: PMC2481299   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0002560   (Journal Full-text)

Sepsis remains a poorly understood, enigmatic disease. One of the cascades crucially involved in its pathogenesis is the complement system. Especially the anaphylatoxin C5a has been shown to have numerous harmful effects during sepsis. We have investigated the impact of high levels of C5a on the adrenal medulla following cecal ligation and puncture (CLP)-induced sepsis in rats as well as the role of C5a on catecholamine production from pheochromocytoma-derived PC12 cells. There was significant apoptosis of adrenal medulla cells in rats 24 hrs after CLP, as assessed by the TUNEL technique. These effects could be reversed by dual-blockade of the C5a receptors, C5aR and C5L2. When rats were subjected to CLP, levels of C5a and norepinephrine were found to be antipodal as a function of time. PC12 cell production of norepinephrine and dopamine was significantly blunted following exposure to recombinant rat C5a in a time-dependent and dose-dependent manner. This impaired production could be related to C5a-induced initiation of apoptosis as defined by binding of Annexin V and Propidium Iodine to PC12 cells. Collectively, we describe a C5a-dependent induction of apoptotic events in cells of adrenal medulla in vivo and pheochromocytoma PC12 cells in vitro. These data suggest that experimental sepsis induces apoptosis of adrenomedullary cells, which are responsible for the bulk of endogenous catecholamines. Septic shock may be linked to these events. Since blockade of both C5a receptors virtually abolished adrenomedullary apoptosis in vivo, C5aR and C5L2 become promising targets with implications on future complement-blocking strategies in the clinical setting of sepsis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
C5RatSepsis  IEP protein:increased activation:plasmaRGD 
C5HumanSepsis  ISOC5 (Rattus norvegicus)protein:increased activation:plasmaRGD 
C5AR1HumanSepsis  ISOC5ar1 (Rattus norvegicus) RGD 
C5ar1RatSepsis  IMP  RGD 
C5ar1MouseSepsis  ISOC5ar1 (Rattus norvegicus) RGD 
HcMouseSepsis  ISOC5 (Rattus norvegicus)protein:increased activation:plasmaRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
C5Ratnegative regulation of dopamine secretion  IDA  RGD 
C5Ratnegative regulation of norepinephrine secretion  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
C5  (complement C5)
C5ar1  (complement C5a receptor 1)

Genes (Mus musculus)
C5ar1  (complement component 5a receptor 1)
Hc  (hemolytic complement)

Genes (Homo sapiens)
C5  (complement C5)
C5AR1  (complement C5a receptor 1)

Objects referenced in this article
Gene C3 complement C3 Homo sapiens
Gene C3 complement component 3 Mus musculus
Gene C3 complement C3 Rattus norvegicus

Additional Information