| First Author | Ulyanova T | Year | 2013 |
| Journal | Haematologica | Volume | 98 |
| Issue | 11 | Pages | 1769-77 |
| PubMed ID | 23812936 | Mgi Jnum | J:293602 |
| Mgi Id | MGI:6450418 | Doi | 10.3324/haematol.2013.087577 |
| Citation | Ulyanova T, et al. (2013) Erythroid cells generated in the absence of specific beta1-integrin heterodimers accumulate reactive oxygen species at homeostasis and are unable to mount effective antioxidant defenses. Haematologica 98(11):1769-77 |
| abstractText | We have previously reported that beta1(Delta/Delta) mice have a markedly impaired response to hemolytic stress, but the mechanisms of this were unclear. In the present study we explored in detail quantitative, phenotypic and functional aspects of erythropoiesis at homeostasis in a large number of animals for each of 3 murine models with specific beta1 heterodimer integrin deficiencies. We found that, at homeostasis, beta1-deficient mice have a modest uncompensated anemia with ineffective erythropoiesis and decreased red blood cell survival. Mice lacking only alpha4 integrins (alpha4beta1/alpha4beta7) do not share this phenotype. There is an increased tendency for reactive oxygen species accumulation in beta1(Delta/Delta) erythroid cells with decreased anti-oxidant defenses at homeostasis which are exaggerated after stress. Furthermore, expansion of erythroid cells in spleen post-stress is dependent on alpha5beta1, likely through mechanisms activating focal adhesion kinase complexes that are distinct from alpha4beta1-mediated responses. In vivo inhibition of focal adhesion kinase activation partially recapitulates the beta1(Delta/Delta) stress response. Mice lacking all alpha4 and beta1 integrins (double knockouts) had, at homeostasis, the most severe phenotype with selective impairment of erythroid responses. The fact that integrins participate in mitigating stress in erythroid cells through redox activation of distinct signaling pathways by specific integrin heterodimers is a link that has not been appreciated until now. |
