This program constitutes a study of the cells and tissues of the hematopoietic system using the methods of cell biology, hematology, and immunology with emphasis on transmission and scanning electron microscopy, freeze-fracture etch and autoradiography. I plan to reassess the phagocytic and fibroblastic properties of cells of the reticuloendothelial system in marrow and spleen using the administration of particulate material and radioactive precursors of collagen and mucopolysaccharides; to study marrow and spleen of Wv and Sl/Sld mice, which have heritable anemias due, respectively, to stem cell deficiency and defects in hematopoietic microenvironment, to continue work on the control of endothelial competence by platelets; to characterize aplastic anemia in mice induced (after a myeloproliferative phase) by x-irradiation, and aplastic anemia in human beings induced therapeutically in preparation for marrow transplantation, or as drug-induced or agnogenic disease; to isolate reticular cells, presumptive fibroblastic cells of the marrow and spleen, and assess their role in inducing hematopoietic cell differentiation and sorting. A major component of this program shall be the study of cell-to-cell interactions, as the passage of maturing hematopoietic cells across the venous endothelium of the bone marrow, the macrophage control of erythropoiesis, the dependence of endothelial structure and competence on a level of circulating blood platelets, the reticular cell interaction with early hematopoietic cells, and the sorting and homing of lymphocytes in spleen and hematopoietic cells and stem cells in marrow.
