| First Author | Zhang LJ | Year | 2019 |
| Journal | Stem Cells | Volume | 37 |
| Issue | 3 | Pages | 430-440 |
| PubMed ID | 30537419 | Mgi Jnum | J:294108 |
| Mgi Id | MGI:6446393 | Doi | 10.1002/stem.2961 |
| Citation | Zhang LJ, et al. (2019) The Impact of Integrin beta2 on Granulocyte/Macrophage Progenitor Proliferation. Stem Cells 37(3):430-440 |
| abstractText | Previously, we reported that although the HSPC frequency in bone marrow cells (BMC) was comparable between beta2-/- and beta2+/+ mice, transplantation of beta2-/- BMC into lethally irradiated CD45.1 recipient resulted in more myeloid cell production than beta2+/+ BMC. The objective of this study is to address if integrin beta2 deficiency skews granulocyte/macrophage progenitor (GMP) proliferation. FACS analysis demonstrated that GMP frequency and cell number were higher and megakaryocyte/erythrocyte progenitor frequency and cell number were lower in beta2-/- mice than beta2+/+ mice. However, the common myeloid progenitors (CMP) frequency and cell number were similar between the two groups. The increased GMP number was due to GMP proliferation as evidenced by the percentage of BrdU-incorporating GMP. Whole genome transcriptome analysis identified increased FcepsilonRIalpha expression in beta2-/- CMP compared to beta2+/+ CMP. FcepsilonRIalpha expression on beta2-/- GMP was detected increased in beta2-/- mice by qRT-PCR and FACS. Although transplantation of FcepsilonRIalpha(hi) GMP or FcepsilonRIalpha(lo) GMP into lethally irradiated CD45.1 recipient resulted in comparable myeloid cell production, transplantation of beta2 deficient FcepsilonRIalpha(hi) GMP generated more myeloid cells than beta2+/+ FcepsilonRIalpha(hi) GMP. GATA2 expression was increased in beta2-/- GMP. Using a luciferase reporter assay, we demonstrated that mutation of the GATA2 binding site in the FcepsilonRIalpha promoter region diminished FcepsilonRIalpha transcription. In vitro, the addition of IgE, the ligand of FcepsilonRIalpha, promoted GMP expansion, which was abrogated by inhibition of JNK phosphorylation. Integrin beta2 deficiency promoted GMP proliferation and myeloid cell production, which was mediated via FcepsilonRIalpha/IgE-induced JNK phosphorylation in GMP. Stem Cells 2019;37:430-440. |
