title: Transendothelial migration enhances integrin-dependent human neutrophil chemokinesis.
abstract: Transendothelial migration of neutrophils induces phenotypic changes that influence the interactions of neutrophils with extravascular tissue components. To assess the influence of transmigration on neutrophil chemokinetic motility, we used polyethylene glycol hydrogels covalently modified with specific peptide sequences relevant to extracellular matrix proteins. We evaluated fMLP-stimulated human neutrophil motility on peptides Arg-Gly-Asp-Ser (RGDS) and TMKIIPFNRTLIGG (P2), alone and in combination. RGDS is a bioactive sequence found in a number of proteins, and P2 is a membrane-activated complex-1 (Mac-1) ligand located in the gamma-chain of the fibrinogen protein. We evaluated, via video microscopy, cell motility by measuring cell displacement from origin and total accumulated distance traveled and then calculated average velocity. Results indicate that although adhesion and shape change were supported by hydrogels containing RGD alone, motility was not. Mac-1-dependent motility was supported on hydrogels containing P2 alone. Motility was enhanced through combined presentation of RGD and P2, engaging Mac-1, alpha(V)beta(3), and beta(1) integrins. Naïve neutrophil motility on combined peptide substrates was dependent on Mac-1, and alpha(4)beta(1) while alpha(6)beta(1) contributed to speed and linear movement. Transmigrated neutrophil motility was dependent on alpha(v)beta(3) and alpha(5)beta(1), and alpha(4)beta(1), alpha(6)beta(1), and Mac-1 contributed to speed and linear motion. Together, the data demonstrate that efficient neutrophil migration, dependent on multi-integrin interaction, is enhanced after transendothelial migration.
authors.affiliation: Leukocyte Biology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2600, USA.
authors.forename: Anjelica L
authors.initials: AL
authors.lastname: Gonzalez
authors.forename: Wafa
authors.initials: W
authors.lastname: El-Bjeirami
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
authors.forename: Larry V
authors.initials: LV
authors.lastname: McIntire
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
mesh_terms: D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D020100:Hydrogels; D016023:Integrins / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D020100:Hydrogels; D016023:Integrins; D009842:Oligopeptides; D010455:Peptides; C524377:Thr-Met-Lys-Ile-Ile-Pro-Phe-Asn-Arg-Thr-Leu-Ile-Gly-Gly; D009240:N-Formylmethionine Leucyl-Phenylalanine; C046617:arginyl-glycyl-aspartyl-serine