title: Rosette nanotubes inhibit bovine neutrophil chemotaxis.
abstract: Migration of activated neutrophils that have prolonged lifespan into inflamed organs is an important component of host defense but also contributes to tissue damage and mortality. In this report, we used biologically-inspired RGD-tagged rosette nanotubes (RNT) to inhibit neutrophil chemotaxis. We hypothesize that RGD-RNT will block neutrophil migration through inhibition of MAPK. In this report, RNT conjugated to lysine (K-RNT) and arginine-glycine-aspartic acid-serine-lysine (RGDSK-RNT) were co-assembled in a molar ratio of 95/5. The effect of the resulting composite RNT (RGDSK/K-RNT) on neutrophil chemotaxis, cell signaling and apoptosis was then investigated. Exposure to RGDSK/K-RNT reduced bovine neutrophil migration when compared to the non-treated group (p<0.001). Similar effect was seen following treatment with ERK1/2 or p38 MAPK inhibitors. Phosphorylation of the ERK1/2 and p38 MAPK was inhibited at 5 min by RGDSK/K-RNT (p<0.05). The RGDSD/K-RNT did not affect the migration of neutrophils pre-treated with αvβ3 integrin antibody suggesting that both bind to the same receptor. RGDSK/K-RNT did not induce apoptosis in bovine neutrophils, which was suppressed by pre-exposing them to LPS (p<0.001). We conclude that RGDSK/K-RNT inhibit phosphorylation of ERK1/2 and p38 MAPK and inhibit chemotaxis of bovine neutrophils.
authors.affiliation: Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
authors.forename: Minh Hong Anh
authors.initials: MH
authors.lastname: Le
authors.forename: Sarabjeet Singh
authors.initials: SS
authors.lastname: Suri
authors.forename: Felaniaina
authors.initials: F
authors.lastname: Rakotondradany
authors.forename: Hicham
authors.initials: H
authors.lastname: Fenniri
authors.forename: Baljit
authors.initials: B
authors.lastname: Singh
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D043942:Nanotubes; D009504:Neutrophils / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D020929:Mitogen-Activated Protein Kinase Kinases