title: The effect of CD47 modified polymer surfaces on inflammatory cell attachment and activation.
abstract: CD47 is a transmembrane protein that is a marker of "self". CD47 binding to its cognate receptor in leukocytes and macrophages, signal-regulatory protein alpha (SIRPα), causes inhibition of inflammatory cell attachment. We hypothesized that immobilization of recombinant CD47 on polymeric surfaces would reduce inflammation. Recombinant CD47 was appended to polyvinyl chloride (PVC) or polyurethane (PU) surfaces via photoactivation chemistry. Cell culture studies showed that CD47 immobilization significantly reduced human neutrophil (HL-60) and human monocyte derived macrophage (MDM) (THP-1) attachment to PVC and PU respectively. A neutralizing antibody, directed against SIRPα, inhibited THP-1 and HL-60 binding to PU and PVC surfaces respectively. This antibody also increased the level of SIRPα tyrosine phosphorylation, thereby indicating a direct role for SIRPα mediated signaling in preventing inflammatory cell attachment. Studies using human blood in an ex vivo flow-loop showed that CD47 modified PVC tubing significantly reduced cell binding and neutrophil activation compared to unmodified tubing or poly-2-methoxy-ethylacrylate (PMEA) coated tubing. In ten-week rat subdermal implants, CD47 functionalized PU films showed a significant reduction in markers of MDM mediated oxidative degradation compared to unmodified PU. In conclusion, CD47 functionalized surfaces can resist inflammatory cell interactions both in vitro and in vivo.
authors.affiliation: Division of Cardiology, Department of Pediatrics, The Children's Hospital of Philadelphia, PA, USA. stachelek@email.chop.edu
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Stachelek
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Finley
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Alferiev
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Wang
authors.forename: Richard K
authors.initials: RK
authors.lastname: Tsai
authors.forename: Edward C
authors.initials: EC
authors.lastname: Eckells
authors.forename: Nancy
authors.initials: N
authors.lastname: Tomczyk
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Connolly
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Discher
authors.forename: David M
authors.initials: DM
authors.lastname: Eckmann
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Levy
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D051928:CD47 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology*; D018922:HL-60 Cells; D006801:Humans; D020007:Implants, Experimental; D007249:Inflammation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D008422:Materials Testing; D015394:Molecular Structure; D010777:Photochemistry / Q000379:methods; D011108:Polymers / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry; D011143:Polyvinyl Chloride / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013499:Surface Properties
chemical_list: D000943:Antigens, Differentiation; D001672:Biocompatible Materials; D051928:CD47 Antigen; D011108:Polymers; D011140:Polyurethanes; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C501920:SIRPA protein, human; D011143:Polyvinyl Chloride