Splenic pooling of granulocytes

Abstract

1. The intrasplenic kinetics of granulocytes, isolated in plasma and labelled in plasma with 111In-tropolonate, have been studied in normal subjects, patients with negative studies for inflammatory disease and patients with positive studies, with the aim of identifying the nature of splenic activity seen after 111In-labelled granulocyte administration. 2. Up to 40 min after injection, 111In activity was visible only in major blood vessels, liver and spleen, with slight, abnormal activity visible in most of those with positive scans. The time courses of uptake of hepatic and splenic activity were different, with liver activity rapidly reaching a plateau and splenic activity increasing mono-exponentially to a plateau achieved between 20 and 40 min. 3. The clear difference between the shapes of the hepatic and splenic uptake curves and the magnitude of the splenic uptake rate constant indicated that splenic activity represented reversible uptake. 4. The application of deconvolution analysis to the blood and splenic time-activity curves generated a splenic retention (or washout) curve consistent with dynamic exchange of granulocytes between blood and spleen. The slope of this curve indicated an intrasplenic granulocyte transit time of 9.3 (±se 0.6) min. 5. Taking splenic activity to be reversible, comparison of the 111In signal from the spleen 40 min after injection of 111In-labelled granulocytes with that given from the spleen after the injection of 111In-labelled erythrocytes (relative to their respective blood levels) indicated that intrasplenic granulocyte transit time was 14.4 (±se 1.1) times that of erythrocytes. Based on actual erythrocyte time, this corresponds to a granulocyte transit time of 8.6-11.5 min, in close agreement with the estimate based on deconvolution analysis. 6. The reversibility of splenic 111In activity after labelled granulocyte injection was confirmed by observing falls in splenic activity between 40 min and 24 h and between 3 and 24 h, which were greater in patients with inflammatory disease than those without. Furthermore, a significant correlation was recorded between this fall and the fraction of the dose of 111In excreted in the faeces in patients with inflammatory bowel disease (IBD). 7. We conclude that the normal spleen contains a reservoir of granulocytes which is in dynamic equilibrium with circulating granulocytes (CGP). This pool therefore is a major component of the body's marginating granulocyte pool (MGP). The mean transit time of granulocytes through the spleen, about 10 min, is remarkably similar to that of platelets.