Adhesion of hematopoietic progenitor cells to human bone marrow or umbilical vein derived endothelial cell lines: a comparison.
Homing of hematopoietic progenitor cells (HPC) to the bone marrow may be mediated by adhesion molecules specifically expressed on human bone marrow endothelial cells (HBMEC). This hypothesis suggests that HPC would preferentially bind to HBMEC compared to endothelial cells from other origins. In this study, HPC were allowed to adhere either to HBMEC cell lines or to human umbilical vein endothelial cells (HUVEC) in two different experimental set-ups. First, adherence was measured using a flow cytometric assay with three different colors identifying each cell population (HPC, HBMEC, HUVEC). HPC could adhere (in a competitive way) to the two endothelial cell lines under stirring conditions, which simulated adhesion under shear stress, as present in blood vessels. Because this assay requires relatively firm adhesion and the endothelial cells don't form a monolayer, we studied the same interactions under less stringent conditions. HPC were allowed to adhere to endothelial monolayers under gently rocking conditions. Differential adhesion of HPC to a set of endothelial cell lines did not correlate with the origin of the endothelial cells. Adhesion of HPC to both types of endothelial cells was inhibited in the presence of various combinations of monoclonal antibodies against the adhesion molecules VLA-4, CD18, and/or E-selectin. No indications were obtained for qualitative differences in the role of these molecules in adhesion of HPC to either HBMEC or HUVEC cell lines. In conclusion, no preferential adhesion of HPC to HBMEC compared to HUVEC cells was observed. This may be due to a lack of origin-specific differences between endothelial cells, implying that the specificity of homing is not regulated at the entrance of the bone marrow. Otherwise, the origin-specific differences between endothelial cells of different origins may be microenvironment-induced, rather then intrinsic, implying that care should be exercised with the use of endothelial cell lines in studies investigating the specificity of homing of HPC.
Rood
P M
PM
CLB, Sanquin Blood Supply Foundation, and Laboratory for Experimental and Clinical Immunology, Academical Medical Center, University of Amsterdam, The Netherlands.
Gerritsen
W R
WR
Kramer
D
D
Ranzijn
C
C
von dem Borne
A E
AE
van der Schoot
C E
CE
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive; D001854:Bone Marrow Cells / Q000166:cytology*; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism; D004727:Endothelium / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D009928:Organ Specificity; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing