A critical role of VLA-4 in erythropoiesis in vivo.
Hematopoiesis requires specific interactions with the microenvironments, and VLA-4 has been implicated in these interactions based on in vitro studies. To study the role of VLA-4 in hematopoiesis in vivo, we performed in utero treatment of mice with an anti-VLA-4 monoclonal antibody. Although all hematopoietic cells in fetal liver expressed VLA-4, the treatment specifically induced anemia. It had no effect on the development of nonerythroid lineage cells, including lymphoids and myeloids. In the treated liver almost no erythroblast was detected, whereas the erythroid progenitors, which give rise to erythroid colonies in vitro, were present. These results indicate that VLA-4 plays a critical role in erythropoiesis, while it is not critical in lymphopoiesis in vivo.
Hamamura
K
K
Second Department of Internal Medicine, Tokyo University, Japan.
Matsuda
H
H
Takeuchi
Y
Y
Habu
S
S
Yagita
H
H
Okumura
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000502:physiology; D005865:Gestational Age; D006411:Hematopoiesis, Extramedullary / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006413:Hematopoietic System / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011247:Pregnancy; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects / Q000196:embryology
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016298:Hematopoietic Cell Growth Factors; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins