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Function of Large and Small Platelets Differs, Depending on Extracellular Calcium Availability and Type of Inductor.

Abstract：

:It is widely anticipated that large platelets are more reactive than small platelets. This was mainly shown in Ca2+-poor media albeit extracellular Ca2+ is utilized by platelets for activation. We determined the impact of extracellular Ca2+ on functional differences between large and small platelets in response to thrombin receptor activating peptide 6 (TRAP-6), adenosine diphosphate (ADP), and epinephrine. In Ca2+-poor buffer, large platelets responded stronger to TRAP-6 which equalized in Ca2+ containing buffer. Large platelets contained and mobilized more Ca2+ from their intracellular stores upon TRAP-6 stimulation explaining their better reactivity in Ca2+-poor media. Stronger aggregation of large platelets in response to ADP also equalized in presence of Ca2+, whereas large platelets responded weaker to ADP in flow cytometry (CD62P-expression: 9.7 mean fluorescence intensity [MFI] [4.4-17.9] vs. 17.5 MFI [6.1-45.6], p = 0.0234) and PAC-1 binding (11.1 MFI [5.7-19.6] vs. 20.5 MFI [14.4-35.0], p = 0.0078). Epinephrine response was stronger in large platelets (CD62P-expression: 11.8 MFI [6.8-33.0] vs. 6.8 MFI [2.5-15.2], p = 0.0078; PAC-1 binding 18.9 MFI [13.6-38.4] vs. 13.0 MFI [6.8-22.4], p = 0.0234; max. aggregation 82.9% [58.7-94.8] vs. 77.2% [19.8-88.8], p = 0.0313), which expressed more α2A receptors. Epinephrine further increased phosphatidylserine (PS) exposure especially in large platelets. PS-positive platelets progressively divided into two subpopulations with high or basic intracellular Ca2+ dependent on extracellular Ca2+. Thrombin generation was faster with small, but accelerated by PS exposure and epinephrine-coactivated large platelets. We show that responses of large and small platelets differ depending on extracellular Ca2+ availability and the inductor. Careful control of extracellular Ca2+ is necessary in functional studies with large and small platelets.

journal_name

Thromb Haemost

journal_title

Thrombosis and haemostasis

authors

Handtke S,Wesche J,Palankar R,Greinacher A,Thiele T

doi

10.1055/s-0040-1712447

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

1075-1086

issue

7

eissn

0340-6245

issn

2567-689X

journal_volume

120

pub_type

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