Stage-specific functional roles of integrins in murine erythropoiesis.
When the erythroid integrins α5β1 and α4β1 were each deleted previously at the stem cell level, they yielded distinct physiologic responses to stress by affecting erythoid expansion and terminal differentiation or only the latter, respectively. To test at what stage of differentiation the integrin effects were exerted, we created mice with α4- or α5-integrin deletions only in erythroid cells and characterized them at homeostasis and after phenylhydrazine-induced hemolytic stress. Unlike our prior data, the phenotype of mice with α5-erythroid deletions was similar to controls, especially after stress. These outcomes seem to reconcile divergent prior views on the role of α5-integrin in erythropoiesis. By contrast, α4 integrins whether deleted early or late have a dominant effect on bone marrow retention of erythroblasts and on terminal erythroid maturation at homeostasis and after stress.
Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA.
Tatyana
T
Ulyanova
Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA.
Steven M
SM
Padilla
Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: thalp@uw.edu.
Thalia
T
Papayannopoulou
D000818:Animals; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D017353:Gene Deletion; D006461:Hemolysis / Q000187:drug effects; D039441:Integrin alpha4 / Q000235:genetics / Q000378:metabolism*; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016877:Oxidants / Q000009:adverse effects / Q000494:pharmacology; D010659:Phenylhydrazines / Q000009:adverse effects / Q000494:pharmacology
D039482:Integrin alpha5; D016877:Oxidants; D010659:Phenylhydrazines; C030299:phenylhydrazine; D039441:Integrin alpha4