The nature and function of granulopoietic microenvironments.
A significant volume of reviewed literature in combination with observations presented here suggest that fibroblastic reticulum cells of the hematopoietic stroma may play a decisive role in the regulation of granulopoiesis. The histology of both bone marrow and spleen demonstrates an association between granulopoiesis and fibroblastic reticulum cells. Using in vitro cultured primary fibroblastic cells from murine bone marrow (BM) as antigenic source, we have prepared a hybridoma cell line secreting a monoclonal antibody (mAb) to fibroblastic reticular cells of the nonlymphoid domains in the spleen and BM. The mAb (ER-HR1) was demonstrated to exclusively detect primary fibroblastic cells cultured from spleen and bone marrow and in situ reticular cells with characteristic dendritic morphology and a dispersed distribution pattern. These reticular cells had extensive ramifications in the hemopoietic parenchyma. With the exception of some sparse fibroblastic cells in the dermis of the skin, the mAb did not react with any other cell type or extracellular substance elsewhere in the mouse, nor did it cross-react with human hemopoietic tissues. Support for a role of fibroblastic reticular cells in the regulation of granulopoiesis was obtained from in vitro studies. Primary BM fibroblasts produced granulocyte-macrophage colony stimulating activity (CSA). In contrast, we have been unable to detect CSA production by BM macrophages. Rather, we have found that BM macrophages deplete exogenous CSA from their culture medium. It is concluded that CSA may be produced by fibroblastic cells in adherent BM cultures and that the low CSA levels detected in their medium is due to depletion of fibroblastic cell-derived CSA by macrophages. We conclude that fibroblastic reticulum cells of the hemopoietic stroma carry unique antigenic determinants and together with macrophages, endothelial cells, and lymphocytes contribute to a complex network of cellular interactions providing an integrated microenvironmental control of granulopoiesis.
D000818:Animals; D000941:Antigens / Q000032:analysis; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D005347:Fibroblasts / Q000166:cytology; D006098:Granulocytes / Q000166:cytology* / Q000502:physiology; D006410:Hematopoiesis; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D010802:Phylogeny; D013154:Spleen / Q000166:cytology / Q000502:physiology
D000941:Antigens