Growth hormone-induced stimulation of multilineage human hematopoiesis.
Growth hormone (GH) has been shown to have significant positive effects on hemato-lymphopoiesis in rodent models and, more recently, to increase thymic mass and circulating naïve CD4+ T cells in humans infected with the human immunodeficiency virus, type 1. To determine whether the latter effects on human T lymphopoiesis might be due, at least in part, to effects on the bone marrow (BM), we examined the specific effects of GH and its proximal mediator, insulin-like growth factor I (IGF-I), on human multilineage hematopoiesis in fetal BM (FBM). Using in vitro analysis, we found that GH and IGF-I each stimulated the expansion of primitive multilineage CD34+CD38- hematopoietic progenitor cells and increased yields of several hematopoietic subpopulations, including CD34+CD38+CD10+ lymphoid progenitor cells. Additionally, GH and IGF-I had direct effects on FBM stromal elements, inducing the expansion of myeloid-like CD45+CD14+ FBM stromal cells and enhancing production of the hematopoietic cytokine interleukin-3 by fibroblast-like CD45-CD10+ FBM stromal cells. Surface expression of GH and type-I IGF receptors correlated with the observed biologic responses to these hormones. Whereas GH enhanced the proliferation of FBM progenitors and stroma, IGF-I exerted a predominantly antiapoptotic effect. Finally, both GH and IGF-I stimulated the generation of hematopoietic colony forming cells. These findings identify specific targets of GH and IGF-I within human FBM, and demonstrate direct and indirect effects that may contribute to GH-mediated enhancement of human hemato-lymphopoiesis.
Hanley
Mary B
MB
Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158-2261, USA.
Napolitano
Laura A
LA
McCune
Joseph M
JM
D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D013006:Growth Hormone / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007377:Interleukin-3 / Q000378:metabolism; D038041:Lymphopoiesis / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000032:analysis; D011986:Receptors, Somatotropin / Q000032:analysis; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D015703:Antigens, CD; D007377:Interleukin-3; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1