Marrow cell egress: specificity of the site of penetration into the sinus.

Blood cells exit the marrow through the wall of the marrow sinuses. Using quantitative electron microscopy of mouse marrow, we addressed two questions regarding the anatomic process of egress: Do leukocytes and reticulocytes exit at specific sites on the sinus wall or do they exit at random loci? Do leukocytes and reticulocytes in egress use a preformed pore or do they make the pore as they exit? We confirmed that exiting leukocytes and reticulocytes do not pass through intercellular junctions; rather they penetrate endothelial cells. The distance of migrating cells from endothelial cell junctions (1.4 ± 0.1 tm) was significantly less (p <0.001) than the distance of endothelial cell junctions from points selected randomly along the sinus waIl (4.0 ± 0.4 sm). The initial stage of cell penetration is often associated with thinning and formation of pits in the endothelial cell. A close-fitting migration pore forms and allows passage of the cell to the sinus lumen. The migration pore of leukocytes reaches a maximum diameter as the middle third of the cell is in transit, whereas the migration pore of reticulocytes is maximal as the first third of the cell is in transit. In sinuses with leukocytes in transit, pores unassociated with migrating cells compose only 10%, whereas pores associated with migrating cells compose 90% of the 25 pores/mm of the sinus wall. In sinuses without cells in transit, pore frequency was only 2/mm. Pores without migrating cells were smaller and were sealed by abluminal adventitial cells. They may represent residues of recent transit. These studies provide quantitative support for a preferential migration site for cells at the parajunctional zone of the endothelial cell and support the concept that pores are made at the time of egress.