Paired immunoglobulin-like receptor B regulates platelet activation

Xuemei Fan, Panlai Shi, Jing Dai, Yeling Lu, Xue Chen, Xiaoye Liu, Kandi Zhang, Xiaolin Wu, Yueping Sun, Kemin Wang, Li Zhu, Chengcheng Zhang, Junfeng Zhang, Guo Qiang Chen, Junke Zheng, Junling Liu

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Murine paired immunoglobulin-like receptors B (PIRB), as the ortholog of human leukocyte immunoglobulin-like receptor B2 (LILRB2), is involved in a variety of biological functions. Here, we found that PIRB and LILRB2 were expressed in mouse and human platelets, respectively. PIRB intracellular domain deletion (PIRB-TM) mice had thrombocythemia and significantly higher proportions of megakaryocytes in bone marrow. Agonist-induced aggregation and spreading on immobilized fibrinogen were facilitated in PIRB-TM platelets. The rate of clot retraction in platelet-rich plasma containing PIRB-TM platelets was also increased. Characterization of signaling confirmed that PIRB associated with phosphatases Shp1/2 in platelets. The phosphorylation of Shp1/2 was significantly downregulated in PIRB-TM platelets stimulated with collagen-related peptide (CRP) or on spreading. The results further revealed that the phosphorylation levels of the linker for activation of T cells, SH2 domain-containing leukocyte protein of 76kDa, and phospholipase C were enhanced in PIRB-TM platelets stimulated with CRP. The phosphorylation levels of FAK Y397 and integrin β3 Y759 were also enhanced in PIRB-TM platelet spread on fibrinogen. The PIRB/LILRB2 ligand angiopoietin-like-protein 2 (ANGPTL2) was expressed and stored in platelet α-granules. ANGPTL2 inhibited agonist-induced platelet aggregation and spreading on fibrinogen. The data presented here reveal that PIRB and its ligand ANGPTL2 possess an antithrombotic function by suppressing collagen receptor glycoprotein VI and integrin αIIbβ3-mediated signaling.

Original languageEnglish (US)
Pages (from-to)2421-2430
Number of pages10
JournalBlood
Volume124
Issue number15
DOIs
StatePublished - Oct 9 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Fan, X., Shi, P., Dai, J., Lu, Y., Chen, X., Liu, X., Zhang, K., Wu, X., Sun, Y., Wang, K., Zhu, L., Zhang, C., Zhang, J., Chen, G. Q., Zheng, J., & Liu, J. (2014). Paired immunoglobulin-like receptor B regulates platelet activation. Blood, 124(15), 2421-2430. https://doi.org/10.1182/blood-2014-03-557645