Cyclophosphamide-induced alterations of bone marrow endothelium: implications in homing of marrow cells after transplantation.
Bone marrow transplantation requires infusion of stem cells i.v. and transport of these cells to the extravascular compartment of the marrow where hemopoiesis takes place. This requires massive cellular traffic across the sinus endothelial barrier. We tested the hypothesis that the conditioning regimen given before transplantation alters the endothelium and permits the traffic of transplanted cells into the hemopoietic compartment. C57B1 mice were given cyclophosphamide i.p. in doses comparable to those used in conditioning regimens. Marrow was perfusion-fixed and studied by electron microscopy at various time after the dose. The salient feature of cyclophosphamide-induced endothelial injury was membrane instability, manifested by sloughing and vesiculation of membrane on the luminal surface. Considerable loss of membrane was associated with a reduction in the surface area of endothelium. There was also an associated loss of integrity of sinus endothelium so that mature circulating red cells, normally confined to the vascular space, could now traverse the vascular wall and appear in the hemopoietic compartment. Moreover, perisinal macrophages, normally confined to extravascular space, were now seen in the lumen. We conclude that the cytotoxic conditioning regimen, given with different objectives, may facilitate the traffic of transplanted cells into the hemopoietic compartment of the marrow.
Shirota
T
T
University of Mississippi School of Medicine, Jackson.
Tavassoli
M
M
D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects* / Q000648:ultrastructure; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D004727:Endothelium / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000187:drug effects
D003520:Cyclophosphamide