Anchoring at an island to relieve stress

To delineate the role of specific members of β1 integrins in stress erythropoiesis in the adult, we compared the response to phenylhydrazine stress in 3 genetically deficient models. The survival of β1-conditionally deficient mice after phenylhydrazine is severely compromised because of their inability to mount a successful life saving splenic erythroid response, a phenotype reproduced in β1Δ/Δ reconstituted animals. The response of bone marrow to phenylhydrazine-induced stress was, unlike that of spleen, appropriate in terms of progenitor cell expansion and mobilization to peripheral blood although late differentiation defects qualitatively similar to those in spleen were present in bone marrow. In contrast to β1-deficient mice, α4Δ/Δ mice showed only a kinetic delay in recovery and similar to β1Δ/Δ, terminal maturation defects in both bone marrow and spleen, which were not present in VCAM-1Δ/Δ mice. Convergence of information from these comparative studies lends new insight to the distinct in vivo roles of α4 and α5 integrins in erythroid stress, suggesting that the presence of mainly α5β1 integrin in all hematopoietic progenitor cells interacting with splenic microenvironmental ligands/cells is instrumental for their survival and accumulation during hemolytic stress, whereas presence of α4, or of both α5 and α4, is important for completion of terminal maturation steps.