title: The macrophage contribution to stress erythropoiesis: when less is enough.
abstract: Although the importance of native bone marrow and spleen macrophages in enhancing baseline and stress erythropoiesis has been emphasized over several decades, their kinetic and phenotypic changes during a variety of stress responses have been unclear. Furthermore, whether monocyte-derived recruited macrophages can functionally substitute for inadequate or functionally impaired native macrophages has been controversial and seem to be not only tissue- but also stress-type dependent. To provide further insight into these issues, we made detailed observations at baseline and post-erythroid stress (E-stress) in 2 mouse models with genetically depressed macrophage numbers and compared them to their controls. We documented that, irrespective of the stress-induced (hemolytic or post-erythropoietin [Epo]) treatment, only native CD11b(lo) splenic macrophages expand dramatically post-stress in normal mice without significant changes in the monocyte-derived CD11b(hi) subset. The latter remained a minority and did not change post-stress in 2 genetic models lacking either Spi-C or VCAM-1 with impaired native macrophage proliferative expansion. Although CD11b(lo) macrophages in these mice were one-fifth of normal at their peak response, surprisingly, their erythroid response was not compromised and was similar to controls. Thus, despite the prior emphasis on numerical macrophage reliance to provide functional rescue from E-stress, our data highlight the importance of previously described non-macrophage-dependent pathways activated under certain stress conditions to compensate for low macrophage numbers.
authors.affiliation: Division of Hematology, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ulyanova
authors.affiliation: Division of Hematology, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Phelps
authors.affiliation: Division of Hematology, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannopoulou
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000008:administration & dosage; D006461:Hemolysis / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010659:Phenylhydrazines / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen / Q000473:pathology; D013312:Stress, Physiological; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C554270:EPO protein, human; D010659:Phenylhydrazines; D011994:Recombinant Proteins; C423918:Spic protein, mouse; D019010:Vascular Cell Adhesion Molecule-1; C030299:phenylhydrazine; D004921:Erythropoietin