title: Effect of a broad-specificity chemokine-binding protein on brain leukocyte infiltration and infarct development.
abstract: OBJECTIVE
  Expression of numerous chemokine-related genes is increased in the brain after ischemic stroke. Here, we tested whether post-stroke administration of a chemokine-binding protein (CBP), derived from the parapoxvirus bovine papular stomatitis virus, might reduce infiltration of leukocytes into the brain and consequently limit infarct development.
  
  
  METHODS
  The binding spectrum of the CBP was evaluated in chemokine ELISAs, and binding affinity was determined using surface plasmon resonance. Focal stroke was induced in C57Bl/6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion for 23 or 47 hours. Mice were treated intravenously with either bovine serum albumin (10 μg) or CBP (10 μg) at the commencement of reperfusion. At 24 or 48 hours, we assessed plasma levels of the chemokines CCL2/MCP-1 and CXCL2/MIP-2, as well as neurological deficit, brain leukocyte infiltration, and infarct volume.
  
  
  RESULTS
  The CBP interacted with a broad spectrum of CC, CXC, and XC chemokines and bound CCL2/MCP-1 and CXCL2/MIP-2 with high affinity (pM range). Stroke markedly increased plasma levels of CCL2/MCP-1 and CXCL2/MIP-2, as well as numbers of microglia and infiltrating leukocytes in the brain. Increases in plasma chemokines were blocked in mice treated with CBP, in which there was reduced neurological deficit, fewer brain-infiltrating leukocytes, and ≈50% smaller infarcts at 24 hours compared with bovine serum albumin-treated mice. However, CBP treatment was no longer protective at 48 hours.
  
  
  CONCLUSIONS
  Post-stroke administration of CBP can reduce plasma chemokine levels in association with temporary atten uation of brain inflammation and infarct volume development.
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Seyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Hannah X
authors.initials: HX
authors.lastname: Chu
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Real
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Saeed
authors.initials: S
authors.lastname: Sharif
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fleming
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Mercer
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Wise
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.).
authors.forename: Grant R
authors.initials: GR
authors.lastname: Drummond
authors.affiliation: From the Department of Pharmacology (S.L., H.X.C., H.A.K., G.R.D., C.G.S.), and Department of Surgery, Southern Clinical School (G.R.D., C.G.S.), Monash University, Clayton, Victoria, Australia; and Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (N.C.R., S.S., S.B.F., A.A.M., L.M.W.). chris.sobey@monash.edu.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
mesh_terms: D000818:Animals; D001921:Brain; D002417:Cattle; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000378:metabolism*; D054426:Chemokine CXCL2 / Q000008:administration & dosage* / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000502:physiology
chemical_list: D054426:Chemokine CXCL2
keywords: chemokine binding protein; chemokines; infarct; ischemia-reperfusion; leukocytes; middle cerebral artery occlusion