Thrombopoietin induces p-selectin expression on platelets and subsequent platelet/leukocyte interactions.
Ligation of thrombopoietin (TPO) to the platelet c-Mpl receptor induces numerous biochemical pathways in the absence of aggregation. Two forms of recombinant TPO are currently in clinical trials for the treatment of thrombocytopenia. This study focuses on the effects of the full-length recombinant human TPO (rhTPO) on platelets in a whole blood system. Platelet-leukocyte associations (PLAs) were visualized following rhTPO stimulation as CD42b/CD 45 double positive clusters by FACS analysis. Treatment of washed platelets with rhTPO induced granule release and expression of the leukocyte adhesion receptor P-selectin (CD 62P) in the absence of aggregation and calcium mobilization. RhTPO also induced platelet-leukocyte interactions in whole blood. Following stimulation, leukocytes were recruited by platelets through P-selectin in a calcium-dependent manner. rhTPO stimulates platelet-leukocyte associations in whole blood through expression of platelet P-selectin. To our knowledge, this is the first report that identifies TPO as a promoter of platelet-leukocyte interactions.
Tibbles
Heather E
HE
Department of Hematology, Parker Hughes Cancer Center, St. Paul, Minnesota 55113, USA.
Navara
Christopher S
CS
Hupke
Michael A
MA
Vassilev
Alexei O
AO
Uckun
Fatih M
FM
D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D019007:P-Selectin / Q000096:biosynthesis*; D010978:Platelet Factor 4 / Q000096:biosynthesis; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; D011994:Recombinant Proteins; D010978:Platelet Factor 4; D013926:Thrombopoietin; D017493:Leukocyte Common Antigens; D002118:Calcium