Expression of receptors for complement anaphylatoxins C3a and C5a following permanent focal cerebral ischemia in the mouse.
In the present study, we have examined the expression of anaphylatoxin C3a and C5a receptors (C3aR and C5aR) at the mRNA and protein levels in ischemic brain tissues following permanent middle cerebral artery (MCA) occlusion in the mouse. C3aR and C5aR mRNAs were both detected by semiquantitative reverse transcription and polymerase chain reaction (RT-PCR) and the cellular distribution of each receptor was analyzed by immunohistochemistry. Significant increases in the expression of C3aR and C5aR mRNAs in the ischemic cortex were observed; the expression of both reached a peak at 2 days after MCA occlusion (4.3- and 3.4-fold increases, respectively, compared with nonoperated control cortical samples; P < 0.00625 with Bonferroni's correction, n = 3). C3aR and C5aR stainings were found constitutively on neurons and astrocytes. In ischemic tissues, we observed that C3aR and C5aR were expressed de novo on endothelial cells of blood vessels, at 6 h and 2 days after MCA occlusion, respectively. C3aR and C5aR immunostaining was increased in macrophage-like cells and reactive astrocytes 7 days postocclusion. C3a and C5a may play an important role in promoting inflammatory and/or repair processes in the ischemic brain by regulating glial cell activation and chemotaxis.
Van Beek
J
J
Faculté Mixte de Médecine et de Pharmacie, European Institute for Peptide Research (IFRMP 23), Rouen Cedex, 76183, France.
Bernaudin
M
M
Petit
E
E
Gasque
P
P
Nouvelot
A
A
MacKenzie
E T
ET
Fontaine
M
M
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics*; D001157:Arterial Occlusive Diseases / Q000276:immunology / Q000378:metabolism; D001923:Brain Chemistry / Q000276:immunology*; D002545:Brain Ischemia / Q000276:immunology / Q000378:metabolism*; D015926:Complement C3a / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism; D017931:DNA Primers; D015870:Gene Expression / Q000276:immunology; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics
D015703:Antigens, CD; D017931:DNA Primers; D008565:Membrane Proteins; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor; D015926:Complement C3a; D015936:Complement C5a