Kinetics of circulating selectin levels during bone marrow aplasia.
We have studied the kinetics of plasma levels of circulating (c)selectins in 8 patients undergoing bone marrow or stem cell transplantation to gain estimates for the distribution and half-life of (c)selectins and to potentially identify an endothelial source of cP-selectin in patients who are deprived of platelets and megakaryocytes. Blood was sampled just before conditioning treatment and immediately after, at 2 occasions under bone marrow aplasia (1 and 2 wk after BMT), on 2 separate days (3-8 d apart) before and at 60 min after platelet transfusion, and 30-72 d after BMT. All (c)selectins showed a strikingly parallel decrease during bone marrow aplasia: cP-selectin decreased by a median of 70% (range: 59-95%), cE-selectin by 63% (range: 27-78%), and cL-selectin by 75% (range: 66-90%) compared to baseline (p=0.012 for all comparisons). Estimates for plasma half-lives of all (c)selectins were obtained from individual time vs. concentration profiles of the maximal decreases and ranged from 2 to 4 d. cP-selectin increased by 23% (p=0.003), cE-selectin by 5% (p=0.041) and cL-selectin by 19% (p=0.009) 1 h after the platelet transfusions. Based on these results the calculated volume of distribution (Vd) of transfused (c)selectins was 2.5-fold higher than the plasma volume, which supports the concept of the in-vivo expression of binding sites, i.e. ligands, for cE-selectin and cL-selectin. In summary, while our study cannot provide any evidence for endothelial cells as a source of cP-selectin, we have found for the first time evidence for the existence of ligands for soluble cE-selectin and cL-selectin in humans.
TARGET-Department of Clinical Pharmacology, University of Vienna, Wien, Austria. bernd.jilma@univie.ac.at
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B
Jilma
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Eichler
A
A
Becherer
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S
Brugger
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P
Kalhs
P
P
Stohlawetz
S
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Kapiotis
S
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Kapiotis
D000328:Adult; D001853:Bone Marrow / Q000002:abnormalities*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis; D002455:Cell Division; D019040:E-Selectin / Q000097:blood; D006801:Humans; D019041:L-Selectin / Q000097:blood; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010976:Platelet Count; D017713:Platelet Transfusion; D011446:Prospective Studies; D019087:Selectins / Q000097:blood* / Q000378:metabolism*; D016037:Single-Blind Method
D019040:E-Selectin; D019007:P-Selectin; D019087:Selectins; D019041:L-Selectin; D002097:C-Reactive Protein