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

Abstract

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.

• Authors: M Schmitt, N Kanayama, A Henschen, A Hollrieder, R Hafter, D Gulba, F Jänicke, H Graeff
• Journal: FEBS letters (FEBS Lett) Vol. 255 Issue 1 Pg. 83-8 (Sep 11 1989) ISSN: 0014-5793 [Print] England
• PMID: 2529137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Chemotactic Factors
• Oligopeptides
• Plasminogen Inactivators
• Proteins
• Serine Proteinase Inhibitors
• Serpins
• eglin proteinase inhibitors
• F-chemotactic peptide
• Plasminogen Activators
• Pancreatic Elastase
• Fibrinolysin
• Urokinase-Type Plasminogen Activator

Topics

• Amino Acid Sequence
• Amino Acids (analysis)
• Binding Sites
• Chemotactic Factors (pharmacology)
• Enzyme Activation (drug effects)
• Fibrinolysin (pharmacology)
• Granulocytes (drug effects, enzymology)
• Humans
• Molecular Sequence Data
• Oligopeptides (pharmacology)
• Pancreatic Elastase (blood, pharmacology)
• Plasminogen Activators (antagonists & inhibitors, metabolism)
• Plasminogen Inactivators
• Proteins
• Serine Proteinase Inhibitors
• Serpins
• Tumor Cells, Cultured (drug effects)
• Urokinase-Type Plasminogen Activator (antagonists & inhibitors, metabolism)