Lactadherin and clearance of platelet-derived microvesicles

Swapan K. Dasgupta, Hanan Abdel-Monem, Polly A. Niravath, Anhquyen Le, Ricardo V. Bellera, Kimberly Langlois, Shigekazu Nagata, Rolando E. Rumbaut, Perumal Thiagarajan

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

The transbilayer movement of phospha-tidylserine from the inner to the outer leaflet of the membrane bilayer during platelet activation is associated with the release of procoagulant phosphatidylserine-rich small membrane vesicles called platelet-derived microvesicles. We tested the effect of lactadherin, which promotes the phagocytosis of phosphatidylserine-expressing lymphocytes and red blood cells, in the clearance of platelet mi-crovesicles. Platelet-derived micro-vesicles were labeled with BODIPY-maleimide and incubated with THP-1-derived macrophages. The extent of phagocytosis was quantified by flow cytometry. Lactadherin promoted phagocytosis in a concentration-dependent manner with a half-maximal effect at approximately 5 ng/mL Lactadherin-deficient mice had increased number of platelet-derived microvesicles in their plasma compared with their wild-type littermates (950 ± 165 vs 4760 ± 650; P = .02) and generated 2-fold more thrombin. In addition, splenic macrophages from lactadherin-deficient mice showed decreased capacity to phagocy-tose platelet-derived microvesicles. In an in vivo model of light/dye-induced endothelial injury/thrombosis in the cremasteric venules, lactadherin-deficient mice had significantly shorter time for occlusion compared with their wild-type littermate controls (5.93 ± 0.43 minutes vs 9.80 ± 1.14 minutes;P = .01). These studies show that lactadherin mediates the clearance of phosphatidylserine-expressing platelet-derived microvesicles from the circulation and that a defective clearance can induce a hypercoagulable state.

Original languageEnglish (US)
Pages (from-to)1332-1339
Number of pages8
JournalBlood
Volume113
Issue number6
DOIs
StatePublished - Feb 5 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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