title: Phenotypic differences of human neutrophils of carriers of the PSGL-1 A and B-allele in binding to immobilised P-selectin under flow conditions.
abstract: P-selectin glycoprotein ligand-1 (PSGL-1) interacts with P-selectin expressed on endothelial cells and platelets. PSGL-1 extracellular mucin-like domain displays a variable number of tandem repeats (VNTRs) polymorphism. The wildtype consists of 16 decameric repeats (designated A isoforms) and variants with 15 (B allele) and 14 (C allele) repeats that are assumed to be associated with reduced risk of vascular disease. We investigated the adhesion of these natural variants to P-selectin in native human neutrophils. Healthy volunteers were genotyped and the adhesion of neutrophils expressing the PSGL-1 isoforms A/A, A/B and B/B were studied under static and physiologic flow conditions. Homozygous B/B neutrophils attached significantly weaker to P-selectin at elevated shear rates from 24 up to 64 dyn/cm(2) than A/A and A/B neutrophils. No difference in adhesion rate was found under static conditions and shear stress below 24 dyn/cm(2), but B/B neutrophils rolled significantly faster than A/A neutrophils at shear stress ≥ 12 dyn/cm(2). There was no difference in the adhesive capacity between A/A an A/B neutrophils. These data support the view that the role of the decamers is to extend the ligand binding domain far above the cell surface to support stable leukocyte adhesion and rolling.
authors.affiliation: Department of Clinical Pharmacology, J.W. Goethe University Hospital Frankfurt/Main, Germany. santos@med.uni-frankfurt.de
authors.forename: Sascha
authors.initials: S
authors.lastname: Meyer dos Santos
authors.forename: Ute
authors.initials: U
authors.lastname: Klinkhardt
authors.forename: Katharina
authors.initials: K
authors.lastname: Lang
authors.forename: Jeannine
authors.initials: J
authors.lastname: Parisius
authors.forename: Karina
authors.initials: K
authors.lastname: Kuczka
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000235:genetics*; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D019007:P-Selectin / Q000097:blood*; D011110:Polymorphism, Genetic; D020033:Protein Isoforms; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D020033:Protein Isoforms