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Relation of Disease Stage to Humoral and Cellular Impairment of Spleen Reticuloendothelial System Depression in a Rat Leukemia¹

Department of Anatomy, Downstate Medical Center, State University of New York, Brooklyn, New York 11203

In the rat leukemia studied there is an early reversible depression of reticuloendothelial system (RES) function followed by a late-stage secondary depression, culminating in death, associated with an inflitration of leukemic cells into the bone marrow and spleen. In one set of experiments to assess RES function, isolated spleens of nonleukemic rats were perfused with blood from rats in progressively advanced stages of the leukemia. In a reciprocal set of experiments, isolated spleens of rats in comparable stages of the leukemia were perfused with blood from nonleukemic rats. The clearance of ^99mTc-sulfur colloid from the blood perfusate was used as a test of RES function. In the first set, clearance was depressed in nonleukemic spleens perfused with blood collected from rats 1 hr after they had been inoculated with tumor cells, and it was more markedly depressed in spleens perfused with blood collected from rats in a late stage of the leukemia 6 days later. Perfusion of nonleukemic spleens with blood from rats in intermediate stages of the leukemia did not depress clearance. In the reciprocal study, clearance was depressed in spleens of rats that were inoculated with tumor cells 1 hr before perfusion with nonleukemic blood. Clearance values were at the control level in spleens of rats in all other stages of the leukemia when calculated on the basis of total spleen weight. When calculated on a unit weight basis, clearance values were lower in the enlarged spleens of rats in advanced stages of the leukemia. The results indicate that impairment of RES clearance of ^99mTc-sulfur colloid is associated with alterations in the humoral content of the blood of this leukemic rat. There is indirect evidence to suggest that in the terminal stage of the leukemia an impairment of splenic RES cells to clear ^99mTc-sulfur colloid may develop secondarily.

¹ Supported by Grant CA 12892-03 from the National Cancer Institute, NIH, and the Mildred Werner League for Cancer Research.

Received 3/29/76. Accepted 7/27/76.