title: The effects of C5aR1 on leukocyte infiltration following pilocarpine-induced status epilepticus.
abstract: This study aimed to determine the role C5aR1 plays in mediating immune responses acutely after pilocarpine-induced status epilepticus (SE), specifically those of brain-infiltrating leukocytes. Three days following pilocarpine SE, we determined by flow cytometry the brain immune cell phenotypes and measured key proinflammatory and antiinflammatory cytokine expression by infiltrating leukocytes and microglia in C5aR1-deficient and wild-type mice. Absence of C5aR1 reduced by 47% the numbers of Ly6G+neutrophils in the brains of No-SE mice and decreased neutrophil entry after SE to levels found in wild-type brains that did not undergo SE (No-SE). Moreover, C5aR1-deficient mice showed increased interleukin (IL)-4 expression in infiltrating leukocytes, but not in microglia. Increases in IL-4 expression in infiltrating leukocytes coupled with decreased neutrophil invasion in C5aR1-deficient mice after SE is likely to contribute to the reduced neuronal loss previously found in these mice compared to their wild-type littermates. Although other SE models need to be investigated to substantiate our findings, this study provides further evidence that C5aR1 is an inflammatory mediator and may play a role in epileptogenesis.
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Benson
authors.affiliation: Department of Sports Medicine, Australian Institute of Sport, Bruce, Australian Capital Territory, Australia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Manzanero
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Karin
authors.initials: K
authors.lastname: Borges
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D015847:Interleukin-4 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects; D018721:Muscarinic Agonists / Q000633:toxicity*; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000235:genetics; D010862:Pilocarpine / Q000633:toxicity*; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
chemical_list: C000591759:C5ar1 protein, mouse; D018721:Muscarinic Agonists; D044087:Receptor, Anaphylatoxin C5a; D010862:Pilocarpine; D015847:Interleukin-4; D017493:Leukocyte Common Antigens
keywords: C5a receptor 1; Complement; Interleukin-4; Neuroinflammation