Adaptation and survival of surface-deprived red blood cells in mice

The consequences of lost membrane area for long-term erythrocyte survival i n the circulation were investigated. Mouse red blood cells were treated wit h lysophosphatidylcholine to reduce membrane area, labeled fluorescently, r einfused into recipient mice, and then sampled periodically for 35 days. Th e circulating fraction of the modified cells decreased on an approximately exponential time course, with time constants ranging from 2 to 14 days. The ratio of volume to surface area of the surviving cells, measured using mic ropipettes, decreased rapidly over the first 5 days after infusion to withi n 5% of normal. This occurred by both preferential removal of the most sphe rical cells and modification of others, possibly due to membrane stress dev eloped during transient trapping of cells in the microvasculature. After 5 days, the cell area decreased with time in the circulation, but the ratio o f volume to surface area remained essentially constant. These results demon strate that the ratio of cell volume to surface area is a major determinant of the ability of erythrocytes to circulate properly.