Phagocytosis and sequestration

Three mechanisms are involved in the action of the spleen: sequestration, phagocytosis and pooling. Sequestration is a reversible process whereby cells are temporarily trapped by adhesion to the reticular meshwork of the cords on their passage through the spleen. Phagocytosis is the irreversible uptake by macrophages of particulate matter, non-viable cells and viable cells which have been damaged by prolonged sequestration or by antibody coating. Pooling is the presence of an increased amount of blood in the spleen in continous exchange with the circulation.

The red cells are subject to a further hazard: as the blood passes through the spleen, the plasma flows freely, whereas the red cells which are trapped in the reticular meshwork have reduced velocity. This leads to a rise in the intrasplenic haematocrit with increased viscosity, resulting in slower flow.

In the presence of metabolically active macrophages, the densely packed red cells are deprived of oxygen and glucose. This stress increases membrane rigidity and reduces the natural deformability of the biconcave cell. This occurs especially as a result of excessive reaction to stress (e.g. because of an underlying abnormality of the red cell metabolic system, or because the cells are already spherical or antibody coated, or are fragmented or misshapen in other ways); they remain trapped in the cord space and there undergo phagocytosis.

Siderotic granules, Howell-Jolly (DNA) bodies, nuclear remnants and Heinz bodies are removed (culling or pitting) during temporary sequestration; after removal of the inclusions, the red cells return to the circulation. Sequestration of reticulocytes has been shown to occur in both humans and in experimental animals. In humans, reticulocytes may be retained in the splenic cords for a considerable proportion of their 2-3 days' maturation time, while they lose their intracellular inclusions, alter the lipid composition of their surface and become smaller in size. It is not clear whether the spleen has any special role at the other end of the life of the red cell in the normal process of elimination of senescent cells; it seems more likely that such cells are removed by the general reticuloendothelial system, including the spleen to some extent, and especially in the marrow.

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