Elastase released from human granulocytes stimulated with N‐formyl‐chemotactic peptide prevents activation of tumor cell prourokinase (pro‐uPA)

FEBS Letters

Graeff, Henner¹  Gulba, Dietrich²  Schmitt, Manfred¹  Henschen, Agnes³  Hollrieder, Angelika¹  Hafter, Reimar¹  Kanayama, Naohiro¹  Jänicke, Fritz¹ 

[1] Frauenklinik der Technischen Universität München, D-8000 München, FRG;Abteilung für Kardiologie der Medizinischen Hochschule Hannover, D-3000 Hannover, FRG;Max-Planck-Institut für Biochemie, D-8033 Martinsried bei München FRG

关键词: Prourokinase;    Plasminogen activator;    Elastase;    Granulocyte;    Chemotactic peptide;    N-terminal amino acid sequence determination;    uPA;    urokinase-type of plasminogen activator;    pro-uPA;    single-chain proenzyme form of urokinase;    HMW-uPA;    two-chain form of high molecular weight urokinase;    BSA;    bovine serum albumin;   

DOI  :  10.1016/0014-5793(89)81065-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Proteolytic enzymes released from granulocytes upon stimulation with the chemotactic N-formyl peptide FNLPNTL (in the presence of cytochalasin B) prevented activation of tumor cell single-chain urokinase-type plasminogen activator (pro-uPA) by plasmin. Elastase was identified by the use of eglin C (elastase inhibitor) and a monoclonal antibody to elastase as the functional proteolytic enzyme in granulocyte supernatants. Action of purified granulocyte elastase on pro-uPA generated enzymatically inactive two-chain uPA linked by disulfide bridges which was indistinguishable by SDS-PAGE from plasmin-generated HMW-uPA. The major elastase cleavage site in pro-uPA was located between Ile¹⁵⁹ and Ile¹⁶⁰; a minor one between Thr¹⁶⁵ and Thr¹⁶⁶. Elastase cannot substitute for plasmin in the proteolytic activation of pro-uPA to enzymatically active HMW-uPA. However, when pro-uPA was first activated by plasmin to form enzymatically active HMW-uPA, this enzymatic activity was not impaired by subsequent elastase treatment.

【 授权许可】

Unknown