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Interactions between the contact system, neutrophils and fibrinogen
1Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140.
Advances in Experimental Medicine and Biology
|January 1, 1990
Summary
High molecular weight kininogen (HK) acts as a receptor on neutrophils, mediating kallikrein binding and enhancing neutrophil activation. Fibrinogen also binds neutrophils via Mac-1, and HK inhibits this fibrinogen-Mac-1 interaction.
Area of Science:
- Immunology
- Hematology
- Biochemistry
Background:
- Plasma kallikrein activates human neutrophils.
- Prekallikrein (PK) circulates complexed with high molecular weight kininogen (HK).
Purpose of the Study:
- To determine if HK mediates kallikrein's association with neutrophils.
- To investigate the interaction between HK, fibrinogen, and neutrophil surface receptors.
Main Methods:
- Investigated 125I-HK and 125I-fibrinogen binding to human neutrophils.
- Assessed cofactor activity of HK for HNE secretion.
- Utilized specific peptides and monoclonal antibodies to identify binding sites and interactions.
Main Results:
- Neutrophils possess surface-membrane binding sites for HK, with specific, saturable, and reversible binding (Kd 9-18 nM).
- HK acts as a cofactor for HNE secretion, with HK-deficient neutrophils showing reduced secretion.
- Fibrinogen binds to neutrophils via Mac-1 (CR3) through its gamma-chain, and HK non-competitively inhibits this binding.
Conclusions:
- Neutrophil surface HK may serve as a receptor for plasma kallikrein.
- Fibrinogen binds to neutrophils through the Mac-1 integrin receptor.
- HK inhibits the interaction between fibrinogen and neutrophil Mac-1.