title: Ligand binding specificity of the leukocyte response integrin expressed by human neutrophils.
abstract: The ligand binding specificity of the leukocyte response integrin (LRI) expressed by polymorphonuclear leukocyte (PMN) was investigated by examining its interaction with two adhesion motifs within fibrinogen: the alpha chain sequence RGD and the gamma chain sequence KQAGDV. The effect of the hexapeptides KQAGDV, KQRGDV, and KGAGDV on fibrinogen-stimulated phagocytosis, a LRI-dependent function, was examined. Surprisingly, the sequence KGAGDV was most potent for inhibition of fibrinogen-stimulated ingestion; the order of potency of these peptides was KGAGDV greater than KQAGDV greater KQRGDV = GRGDSPA. Latex spheres coated with multivalent KGAGDV bound specifically to PMN and antibodies that recognized either the LRI beta chain (7G2) or an associated protein (IAP)-abrogated bead binding. Various control and anti-beta 1 and anti-beta 2 antibodies did not affect bead binding. Monovalent peptides KGAGDV and KQRGDV were equipotent for inhibition of bead binding to unstimulated PMN (ID50 = 19 microM). In contrast, KGAGDV was more potent than KQRGDV for inhibition of bead binding to N-formylmethionylleucylphenylalanine-stimulated PMN (ID50 = 2.5 microM versus ID50 = 60 microM). A control peptide, KGALEVA, did not inhibit LRI ligand binding or function. These data suggest that the unique amino acid sequence KGAGDV may represent a specific ligand for LRI and that LRI ligand binding specificity may be regulated by the activation state of the cell.
authors.affiliation: Department of Pharmacology, University of Missouri, Columbia.
authors.forename: H D
authors.initials: HD
authors.lastname: Gresham
authors.forename: S P
authors.initials: SP
authors.lastname: Adams
authors.forename: E J
authors.initials: EJ
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D005340:Fibrinogen / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007700:Kinetics; D007797:Laminin / Q000494:pharmacology; D008024:Ligands; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000911:Antibodies, Monoclonal; D016023:Integrins; D007797:Laminin; D008024:Ligands; D046911:Macromolecular Substances; D009842:Oligopeptides; C075596:integrin, leukocyte response; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005340:Fibrinogen