Elastin derived peptides protect elastic fibres degradation by human neutrophil elastase: in vitro and in vivo studies using a mechanically induced rat gingival inflammatory model.
An elastin peptide (kE57) obtained from organoalkaline hydrolysis of calf ligamentum nuchae insoluble elastin, was isolated by gel permeation on Sephadex G150 and high performance liquid chromatography on a TSK G 3000 SW column. It possessed an average Mr = 57,000 and similar amino acids composition as its insoluble counterpart. kE57 behave as a competitive inhibitor of human neutrophil elastase (HNE) with Ki = 1.4 microM; it also inhibited porcine pancreatic elastase (PPE) but less efficiently Ki = 180 microM. Identification of elastic fibres in rat gingiva was ascertained by light and electron microscopic studies. Morphometric studies indicated that rat gingiva contained similar levels of elastic fibres (= 2%) as human skin; elastic fibres networks from both tissues also displayed high structural analogy. Gingival chronic inflammation was induced in rats by mechanical impaction associated with an hyperglucidic diet. After 5 weeks, the levels of rat gingiva elastic fibres, decreased from Vv = 1.94 +/- 0.1% to Vv = 1.02 +/- 0.06%. Local injections of kE57: 100 micrograms per day, 5 days a week for 5 weeks did restore the integrity of the gingiva elastic fibres network: Vv = 1.84 +/- 0.1. Without influencing leucocyte infiltration, it is proposed that elastin-derived peptides, acting as potent competitive inhibitor of neutrophil elastase involved in periodontitis, might be of therapeutic value.
Bonnaure-Mallet
M
M
Equipe de Biologie Buccale, UFR d'Odontologie, Rennes, France.
Godeau
G
G
Tixier
J M
JM
Lebon-Pelletier
P
P
Chambon
Y
Y
Robert
L
L
Hornebeck
W
W
D000818:Animals; D002417:Cattle; D002908:Chronic Disease; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000378:metabolism* / Q000473:pathology; D004549:Elastin / Q000302:isolation & purification / Q000494:pharmacology*; D005891:Gingivitis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019272:Leukocyte Elastase; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010446:Peptide Fragments / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D013552:Swine
D010446:Peptide Fragments; D004549:Elastin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase