title: Proteolytic cleavage of annexin 1 by human leukocyte elastase.
abstract: Annexin 1 has been shown to participate through its unique N-terminal domain in the recruitment and activation of leukocytes at sites of inflammation. Peptides derived from this domain are true mimetics of the annexin 1 action in all inflammation models tested and most likely serve as the active entities generated at sites of inflammation. To elucidate mechanisms underlying peptide generation we used isolated blood leukocytes and endothelial cell monolayers. We show that following endothelial adhesion, annexin 1 was externalized from leukocytes and rapidly cleaved. Addition of purified annexin 1 to degranulating leukocytes resulted in the truncation of annexin 1, which seemed to depend on the proteolytic activity of human leukocyte elastase (HLE). The capacity of elastase to proteolytically cleave annexin 1 was confirmed using both purified annexin 1 and HLE. The identification of annexin 1 as a substrate for HLE supports the model in which annexin 1 participates in regulating leukocyte emigration into inflamed tissue through N-terminal peptides generated at inflammatory sites.
authors.affiliation: Center for Molecular Biology of Inflammation, Institute for Medical Biochemistry, von Esmarch-Strasse 56, 48149 Münster, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Rescher
authors.forename: Verena
authors.initials: V
authors.lastname: Goebeler
authors.forename: Andreas
authors.initials: A
authors.lastname: Wilbers
authors.forename: Volker
authors.initials: V
authors.lastname: Gerke
mesh_terms: D017305:Annexin A1 / Q000737:chemistry* / Q000378:metabolism*; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D019272:Leukocyte Elastase / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D021381:Protein Transport; D013379:Substrate Specificity
chemical_list: D017305:Annexin A1; D019272:Leukocyte Elastase