SWAP-70 regulates erythropoiesis by controlling α4 integrin

Haematologica. 2011 Dec;96(12):1743-52. doi: 10.3324/haematol.2011.050468. Epub 2011 Aug 31.

Abstract

Background The regulation of normal and stress-induced erythropoiesis is incompletely understood. Integrin-dependent adhesion plays important roles in erythropoiesis, but how integrins are regulated during erythropoiesis remains largely unknown.

Design and methods: To obtain novel insights into the regulation of erythropoiesis, we used cellular and molecular approaches to analyze the role of SWAP-70 and the control of integrins through SWAP-70. In addition, mice deficient for this protein were investigated under normal and erythropoietic stress conditions.

Results: We show that SWAP-70, a protein involved in cytoskeletal F-actin rearrangements and integrin regulation in mast cells, is expressed in hematopoietic stem cells and myeloid-erythroid precursors. Although Swap-70(-/-) mice are not anemic, erythroblastic differentiation is perturbed, and SWAP-70 is required for an efficient erythropoietic stress response to acute anemia and for erythropoietic recovery after bone marrow transplantation in irradiated mice. SWAP-70 deficiency impairs colony-forming unit erythroid development, while burst-forming unit erythroid development is normal, and significantly affects development of late erythroblasts in the spleen and bone marrow. The α(4) integrin is constitutively hyper-activated in Swap-70(-/-) colony-forming unit erythroid cells, which hyper-adhere to fibronectin. Blocking α(4) and β(1) integrin chains in vivo restored erythroblastic differentiation and the erythropoietic stress response in Swap-70(-/-) mice. Conclusions Our study reveals that SWAP-70 is a novel regulator of integrin-mediated red blood cell development and stress-induced erythropoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Anemia / genetics
  • Anemia / metabolism
  • Animals
  • Cell Adhesion / physiology
  • Cell Differentiation / physiology*
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Erythroblasts / cytology
  • Erythroblasts / metabolism*
  • Erythropoiesis / physiology*
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Integrin alpha4 / genetics
  • Integrin alpha4 / metabolism*
  • Mice
  • Mice, Knockout
  • Minor Histocompatibility Antigens
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*

Substances

  • Actins
  • DNA-Binding Proteins
  • Fibronectins
  • Guanine Nucleotide Exchange Factors
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • Swap70 protein, mouse
  • Integrin alpha4