Complement anaphylatoxin C3a is selectively protective against NMDA-induced neuronal cell death.
The anaphylatoxin C3a is a potent inflammatory polypeptide released at sites of complement activation. To test whether C3a might alter neuronal outcome following an ischemic insult, we determined the effects of purified human C3a on murine primary cortical cell cultures exposed to apoptotic or excitotoxic paradigms. C3a prevented neither serum deprivation-induced apoptotic neuronal death, nor AMPA/kainate-mediated excitotoxicity. However, in mixed cultures of neurons and astrocytes, C3a dose-dependently protected neurons against NMDA toxicity (47% neuroprotection using 100 nM C3a, p < 0.01, n = 12). The neuroprotective effect of C3a was observable only in the presence of astrocytes. These observations suggest that C3a is involved in excitotoxicity-mediated neuronal death through astrocyte stimulation and extend its role beyond immune functions.
van Beek
J
J
European Institute for Peptide Research (IFRMP 23), INSERM U519, Rouen, France. van_beek@hotmail.com
Nicole
O
O
Ali
C
C
Ischenko
A
A
MacKenzie
E T
ET
Buisson
A
A
Fontaine
M
M
D000706:Anaphylatoxins / Q000032:analysis / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D015926:Complement C3a / Q000032:analysis / Q000235:genetics*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D015870:Gene Expression / Q000502:physiology; D006168:Guinea Pigs; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis
D000706:Anaphylatoxins; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D012333:RNA, Messenger; D016202:N-Methylaspartate; D015926:Complement C3a