Effect of protein synthesis inhibition by cycloheximide on lymphocyte circulation.
BACKGROUND
Lymphocyte recirculation is directed by glycoprotein adhesion 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 study, the effects of inhibiting new protein synthesis on the ability of lymphocytes to circulate and home to different lymphoid tissues was investigated.


METHODS
New Zealand White rabbits and Lewis white rats were treated with cycloheximide or buffer. Total circulating lymphocyte counts and lymphocyte subsets were measured. Rabbits were given autologous, 111indium-labeled lymphocytes to determine if there were changes in the organ distribution of lymphocytes after cycloheximide 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 distribution of the radiolabeled, autologous lymphocytes in cycloheximide-treated animals showed significantly greater numbers circulating in the peripheral blood and decreased numbers in Peyer's patches, mesenteric 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 that protein synthesis inhibition causes lymphocytosis due to decreased lymphocyte homing to mesenteric nodes, Peyer's patches, and spleen, but not lung. This effect was not specific for distinct lymphocyte subsets, including T cells, B cells, or lymphocytes expressing L-selectin. These data show that molecules modulating lymphocyte homing in some organs have rapid turnover rates and suggest that changes in homing during the inflammatory process can be rapidly regulated by changes in protein translation.
Wiebke
J L
JL
Department of Pediatrics, Indiana University, Indianapolis.
Quinlan
W M
WM
Graham
L
L
Doerschuk
C M
CM
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000097:blood; D002465:Cell Movement / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology*; D005260:Female; D019041:L-Selectin; D007958:Leukocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008221:Lymphoid Tissue / Q000166:cytology* / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew
D015815:Cell Adhesion Molecules; D011506:Proteins; D019041:L-Selectin; D003513:Cycloheximide