title: RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation.
abstract: Rosette nanotubes (RNT) are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif). In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C) and amino acid Lys (K-G∧C) which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as K(x)/RGDSK(y)-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK-G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous K(x)/RGDSK(y)-RNT on acute lipopolysaccharide (LPS)-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 μg and/or intravenously with K⁹⁰/RGDSK¹⁰-RNT. Here we provide the first evidence that intravenous administration of K⁹⁰/RGDSK¹⁰-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K⁹⁰/RGDSK¹⁰-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K⁹⁰/RGDSK¹⁰-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1β, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K⁹⁰/RGDSK¹⁰-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.
authors.affiliation: Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Sarabjeet Singh
authors.initials: SS
authors.lastname: Suri
authors.forename: Steven
authors.initials: S
authors.lastname: Mills
authors.forename: Gurpreet Kaur
authors.initials: GK
authors.lastname: Aulakh
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; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D043942:Nanotubes / Q000737:chemistry* / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects; D009842:Oligopeptides / Q000737:chemistry* / Q000633:toxicity; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D009195:Peroxidase