Ligand binding specificity of the leukocyte response integrin expressed by human neutrophils.
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.
Gresham
H D
HD
Department of Pharmacology, University of Missouri, Columbia.
Adams
S P
SP
Brown
E J
EJ
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
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