EFFECT OF PROTEIN-SYNTHESIS INHIBITION BY CYCLOHEXIMIDE ON LYMPHOCYTECIRCULATION

BACKGROUND: Lymphocyte recirculation is directed by glycoprotein adhes ion molecules on lymphocytes and endothelial cells of lymphoid tissues . Lymphocyte circulation in different lymphoid tissues is dependent on the type of glycoprotein adhesion molecules present. In the present s tudy, the effects of inhibiting new protein synthesis on the ability o f lymphocytes to circulate and home to different lymphoid tissues was investigated. EXPERIMENTAL DESIGN: New Zealand White rabbits and Lewis white rats were treated with cycloheximide or buffer. Total circulati ng lymphocyte counts and lymphocyte subsets were measured. Rabbits wer e given autologous, (111)indium-labeled lymphocytes to determine if th ere were changes in the organ distribution of lymphocytes after cycloh eximide treatment. RESULTS: After cycloheximide treatment, the number of circulating lymphocytes but not neutrophils increased significantly by 2 hours in both rabbits and rats. T cells, B cells, and L-selectin -positive lymphocytes showed similar increases. Measurements of the di stribution of the radiolabeled, autologous lymphocytes in cycloheximid e-treated animals showed significantly greater numbers circulating in the peripheral blood and decreased numbers in Peyer's patches, mesente ric lymph nodes, and spleens compared with controls. In contrast, the number of radiolabeled lymphocytes in the lung was not decreased after cycloheximide administration. CONCLUSIONS: These results indicate tha t protein synthesis inhibition causes lymphocytosis due to decreased l ymphocyte homing to mesenteric nodes, Peyer's patches, and spleen, but not lung. This effect was not specific for distinct lymphocyte subset s, including T cells, B cells, or lymphocytes expressing L-selectin. T hese data show that molecules modulating lymphocyte homing in some org ans have rapid turnover rates and suggest that changes in homing durin g the inflammatory process can be rapidly regulated by changes in prot ein translation.