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High susceptibility to ADP-induced thrombus formation in mast cell-deficient W/Wv mice
Abstract:
We used mast cell-deficient W/Wv mice to clarify whether mast cell-derived heparin may play a role in inhibiting thrombus formation in the living organism. Small veins in the mesentery of W/Wv or congenic +/+ mice were stretched over an inverted microscope; a micropipette filled with varying concentrations of ADP was set close to the outside of a vein by using a micromanipulator. Thrombus formation was directly examined under the microscope. The concentration of ADP necessary for thrombus formation was significantly lower in the W/Wv mice than in the congenic +/+ mice. Furthermore, the concentration of ADP necessary for aggregation of platelets in platelet-rich plasma (PRP) was significantly lower in W/Wv mice than in +/+ mice. The higher sensitivity of PRP of W/Wv mice is not attributed to the platelets, but to the plasma, since platelets of +/+ mice suspended in platelet-poor plasma (PPP) of W/Wv mice were more sensitive to ADP than platelets of W/Wv mice suspended in PPP of +/+ mice. The present results suggest that plasma of W/Wv mice may lack any inhibitory factor(s) or contain promoting factor(s) for platelet aggregation.
Insights
Mast cell-deficient mice show increased thrombus formation, indicating heparin may inhibit clot development. Their plasma, not platelets, drives this heightened sensitivity to adenosine diphosphate (ADP).
Area of Science:
- Hematology
- Immunology
- Physiology
Background:
- Mast cells are implicated in various physiological processes.
- Heparin, a substance derived from mast cells, is known for its anticoagulant properties.
- The precise role of mast cell-derived heparin in inhibiting thrombus formation in vivo remains unclear.
Purpose of the Study:
- To investigate the role of mast cell-derived heparin in inhibiting thrombus formation.
- To determine if mast cell deficiency affects the sensitivity to adenosine diphosphate (ADP)-induced thrombus formation.
Main Methods:
- Utilized mast cell-deficient W/Wv mice and congenic +/+ mice.
- Observed thrombus formation in mesenteric veins using an inverted microscope.
- Administered varying concentrations of ADP via micropipette to induce thrombus formation.
- Assessed platelet aggregation in platelet-rich plasma (PRP) and platelet-poor plasma (PPP).
Main Results:
- Significantly lower concentrations of ADP were required to induce thrombus formation in W/Wv mice compared to +/+ mice.
- Platelet-rich plasma (PRP) from W/Wv mice showed significantly lower ADP-induced aggregation compared to +/+ mice.
- The heightened sensitivity was attributed to plasma factors, not platelets, as +/+ platelets in W/Wv plasma were more sensitive to ADP.
Conclusions:
- Mast cell-derived heparin may play a crucial role in inhibiting thrombus formation.
- Plasma from mast cell-deficient mice exhibits increased susceptibility to platelet aggregation.
- This suggests a potential deficiency in inhibitory factors or presence of promoting factors in the plasma of W/Wv mice.