title: Release of a new vascular permeability enhancing peptide from kininogens by human neutrophil elastase.
abstract: Stimulated neutrophils produced vascular permeability enhancing (VPE) activity in the presence of high molecular weight kininogen (HMWK), which was inhibited mainly by a neutrophil elastase (NE) inhibitor or a bradykinin (BK) B(2)-receptor antagonist. NE (>3 nM) generated VPE activity from kininogens at normal plasma concentrations with the smaller protein being several fold more responsive than the larger protein, through releasing a new VPE peptide (E-kinin), SLMKRPPGFSPFRSSRI. Synthetic E-kinin, SLMKRPPGFSPFRSS and SLMKRPPGFSPFR had VPE and blood pressure lowering activities, which were comparable to the activities of BK and completely inhibited by B(2)-receptor antagonists. Interestingly, E-kinin and SLMKRPPGFSPFRSS did not induce smooth muscle contraction. These results suggest that E-kinin formed in vivo may be processed at the carboxy-terminus to give a peptide that can bind to the B(2)-receptor. The molecular mechanism for neutrophil-associated VPE may be explained by excision of E-kinin from kininogens by NE, followed by further processing of the peptide.
authors.affiliation: Division of Molecular Pathology, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, 2-2-1, Honjo, Kumamoto 860-0811, Japan. taka@kaiju.medic.kumamoto-u.ac.jp
authors.forename: Takahisa
authors.initials: T
authors.lastname: Imamura
authors.forename: Sumio
authors.initials: S
authors.lastname: Tanase
authors.forename: Izumi
authors.initials: I
authors.lastname: Hayashi
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kozik
authors.forename: James
authors.initials: J
authors.lastname: Travis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000378:metabolism; D019728:Kininogen, Low-Molecular-Weight / Q000378:metabolism; D007704:Kininogens / Q000378:metabolism*; D007705:Kinins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2
chemical_list: D065168:Bradykinin Receptor Antagonists; C459593:E kinin; D004791:Enzyme Inhibitors; D019679:Kininogen, High-Molecular-Weight; D019728:Kininogen, Low-Molecular-Weight; D007704:Kininogens; D007705:Kinins; D010455:Peptides; D043782:Receptor, Bradykinin B2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019272:Leukocyte Elastase; D001920:Bradykinin