International Journal of Hematology

DOI: 10.1007/s12185-019-02680-4 Pages: 285-294

Soluble CLEC-2 is generated independently of ADAM10 and is increased in plasma in acute coronary syndrome: comparison with soluble GPVI

1. University of Yamanashi, Infection Control Office, University of Yamanashi Hospital, Faculty of Medicine

2. University of Yamanashi, Department of Clinical and Laboratory Medicine, Faculty of Medicine

3. Gunma Paz University, Graduate School of Health Science

4. LSI Medience Corporation, Department of Antibody Group, Narita R&D Department, Research and Development Division

5. University of Yamanashi, Department of Health Sciences, Interdisciplinary Graduate School of Medicine and Engineering

6. Juntendo University School of Medicine, Department of Cardiovascular Medicine

7. University of Tokyo, Department of Laboratory Medicine, Graduate School of Medicine

8. Japan Society for the Promotion of Science

9. Fuefuki Chuo Hospital

Correspondence to:
Katsue Suzuki-Inoue
Tel: +81-55-273-9884



Soluble forms of platelet membrane proteins are released upon platelet activation. We previously reported that soluble C-type lectin-like receptor 2 (sCLEC-2) is released as a shed fragment (Shed CLEC-2) or as a whole molecule associated with platelet microparticles (MP-CLEC-2). In contrast, soluble glycoprotein VI (sGPVI) is released as a shed fragment (Shed GPVI), but not as a microparticle-associated form (MP-GPVI). However, mechanism of sCLEC-2 generation or plasma sCLEC-2 has not been fully elucidated. Experiments using metalloproteinase inhibitors/stimulators revealed that ADAM10/17 induce GPVI shedding, but not CLEC-2 shedding, and that shed CLEC-2 was partially generated by MMP-2. Although MP-GPVI was not generated, it was generated in the presence of the ADAM10 inhibitor. Moreover, antibodies against the cytoplasmic or extracellular domain of GPVI revealed the presence of the GPVI cytoplasmic domain, but not the extracellular domain, in the microparticles. These findings suggest that most of the GPVI on microparticles are induced to shed by ADAM10; MP-GPVI is thus undetected. Plasma sCLEC-2 level was 1/32 of plasma sGPVI level in normal subjects, but both soluble proteins significantly increased in plasma of patients with acute coronary syndrome. Thus, sCLEC-2 and sGPVI are released by different mechanisms and released in vivo upon platelet activation.

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