Impact of carbamylation on type I collagen conformational structure and its ability to activate human polymorphonuclear neutrophils.
Carbamylation by urea-derived cyanate is a posttranslational modification of proteins increasing during chronic renal insufficiency, which alters structural and functional properties of proteins and modifies their interactions with cells. We report here the major structural alterations of type I collagen induced by carbamylation. Biophysical methods revealed that carbamylated collagen retained its triple-helical structure, but that slight changes destabilized some regions within the triple helix and decreased its ability to polymerize into normal fibrils. These changes were associated with the incapacity of carbamylated collagen to stimulate polymorphonuclear neutrophil oxidative functions. This process involved their interaction with LFA-1 integrin, but no subsequent p(125)FAK phosphorylation. Carbamylation of collagen might alter interactions between collagen and inflammatory cells in vivo and interfere with the normal remodeling of extracellular matrix, thus participating in the pathophysiological processes occurring during renal insufficiency.
Laboratory of Medical Biochemistry and Molecular Biology, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6198, Faculty of Medicine, University of Reims Champagne-Ardenne, France.
Stéphane
S
Jaisson
Sandrine
S
Lorimier
Sylvie
S
Ricard-Blum
Ganesh D
GD
Sockalingum
Céline
C
Delevallée-Forte
Gregory
G
Kegelaer
Michel
M
Manfait
Roselyne
R
Garnotel
Philippe
P
Gillery
D002942:Circular Dichroism; D024042:Collagen Type I / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008855:Microscopy, Electron, Scanning; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman
D024042:Collagen Type I