title: Fibrinogen-mediated epidermal cell migration: structural correlates for fibrinogen function.
abstract: Previously we showed that epidermal cells are able to use fibrinogen (FGN) as a migration substratum during wound closure. The goal of the present study was to determine the structural features of FGN that allow this migration. Pieces of glass coated with native, fragmented, or other modified forms of FGN were implanted into full-thickness skin wounds of adult newts such that migrating epidermal cells would encounter the implant. In this system, a coating of FGN allowed considerably more migration than a coating of BSA. At high concentrations, heat-denatured FGN supported as much migration as the same amount of intact FGN. Fraction I-9, a circulating form of FGN missing a 20-30K (K = 10(3) Mr) carboxy-terminal segment of the A alpha chain, was no less effective than intact FGN. Comparison of the isolated D1 and E fragments of FGN showed migration only on D1, but never to the extent seen on intact FGN containing the same amount of D1. Plasmin digestion of D1 in the presence of EDTA, a process which produces D3, a fragment differing from D1 by the loss of the carboxy-terminal 109 amino acids of the gamma chain, caused a significant loss of activity in the D fragment. Migration was good on implants coated with relatively high concentrations of purified A alpha chains but gamma chains were inactive. Migration over intact FGN was almost totally blocked by 230 microM-Arg-Gly-Asp-Ser (RGDS), a peptide known to interact with integrin-type receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anatomy and Neurobiology, Health Science Center, University of Tennessee, Memphis 38163.
authors.forename: D J
authors.initials: DJ
authors.lastname: Donaldson
authors.forename: J T
authors.initials: JT
authors.lastname: Mahan
authors.forename: D
authors.initials: D
authors.lastname: Amrani
authors.forename: J
authors.initials: J
authors.lastname: Hawiger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D005340:Fibrinogen / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D012455:Salamandridae; D013329:Structure-Activity Relationship; D014945:Wound Healing / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D005340:Fibrinogen