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Thrombin-mediated events implicated in mast cell activation
S M Strukova1, T N Dugina, S V Khlgatian
1Department of Human Physiology, Faculty of Biology, Moscow State University, Russia.
Seminars in Thrombosis and Hemostasis
|January 1, 1996
Summary
Peritoneal mast cells (PMCs) show distinct responses to various thrombin forms, suggesting multiple thrombin receptors. These receptors influence ion exchange, pH, cyclic guanosine monophosphate (cGMP) levels, and histamine release.
Area of Science:
- Immunology
- Biochemistry
- Cell Biology
Background:
- Mast cells are implicated in immune responses.
- Thrombin's role in mast cell activation is suggested by heparin release.
- Understanding mast cell receptors for thrombin is crucial for inflammatory pathway research.
Purpose of the Study:
- To investigate peritoneal mast cell (PMC) responsiveness to different forms of thrombin.
- To elucidate the mechanisms of thrombin-induced mast cell activation.
- To identify potential thrombin receptor subtypes on PMCs.
Main Methods:
- Measurement of ion conductance, intracellular pH, and cyclic guanosine monophosphate (cGMP) concentration.
- Quantification of histamine release from PMCs.
- Exposure of PMCs to alpha-thrombin, diisopryopyl-phosphoryl-alpha-thrombin (DIP-alpha-thrombin), and gamma-thrombin.
Main Results:
- PMCs activated Na/H exchange and increased cell conductance/capacitance in response to alpha-thrombin and DIP-alpha-thrombin, but not gamma-thrombin.
- Alpha-thrombin induced cytoplasmic acidification (in Ca-free medium) and biphasic pH changes at higher doses.
- Low alpha-thrombin concentrations (< 1 nmol/L) increased cGMP and decreased histamine release, while high concentrations (> 1 mumol/L) accelerated histamine release.
Conclusions:
- Results suggest the presence of multiple thrombin receptors on PMCs with distinct signaling pathways.
- Different thrombin forms differentially activate mast cell responses, including ion transport and mediator release.
- The findings provide insights into the complex interaction between thrombin and mast cells, impacting histamine release and cellular signaling.