This study is concerned with: (1) the mechanism involved in the transmural passage of blood cells from the extravascular site of formation into the peripheral pool; (2) the possible disturbance in this transmural passage in myelogenous leukemia; (3) the entry into the circulation of cells of malignant tumors (leukemic and non-leukemic) in the first phase of metastases formation; (4) the subsequent organ disposition of the intravascular malignant cells; (5) the endocytosis and intracellular disposition of exogenous and endogenous proteins in the sinus endothelia of bone marrow and liver; and (6) the surface characteristics and changes in the surface characteristics of the cellular elements involved in the above processes. It was found that the entry of the extravascularly matured blood cells into the intravascular space is through the cell body of the endothelial sinus cell and not through preformed pores. That is, the transmural passage of blood cells is transcellular. This is true for the bone marrow under both normal and leukemic conditions. The transmural passage is accompanied by the accumulation of a non-sialated cationic substance at the advancing margin of the migrating cell. The entry of lymphatic cells into the circulation as well as the return of lymphocytes into the lymphatic parenchyma is similarly a transcellular process. The entry into the circulation of malignant cells in the first phase of metastases formation can take place through the intact vascular endothelium and follows a transcellular pathway. The surface characteristics of the sinus endothelium of the bone marrow changes at sites of functional modification; the endocytic bristle-coated pits and the diaphragmed fenestrae are, in contrast to the non-modified cell surface, free from sialated complex polysaccharides. The endocytosis of exogenous and endogenous proteins and non-proteinaceous tracers by the sinus endothelia of bone marrow and liver is effected through bristle-coated pits. Through a series of membrane fusions, the endocytosed material is deposited in the vascular apparatus. (L)
