The Influence of the Spleen on Neutrophil Apoptosis In Vivo

In contrast to radiolabelled erythrocytes and platelets, radiolabelled neutrophils leave the circulating blood in an exponential manner, indicating random rather than age-dependent removal. Neutrophils transit the spleen with a range of residence times that are log normally distributed. We hypothesized that neutrophils are conditioned to undergo apoptosis to an extent that depends on their intrasplenic residence time and that this provides an explanation for the random removal of these cells from blood. Splenic venous and peripheral arterial blood was sampled simultaneously during abdominal surgery in four patients and age-dependent apoptosis assessed in whole blood using annexin V/PI staining. Apoptosis increased after 4 and 20 h ex-vivo incubation and was invariably higher in splenic venous vs arterial neutrophils. Transit through the spleen appears to promote neutrophil apoptosis, with subsequent high efficiency clearance by the liver. This may explain the mechanism underlying the random removal of neutrophils from the blood.