Apoptosis of peripheral blood lymphocytes is induced by catecholamines.
We explored the mechanism through which patients sometimes show immunosuppression after cardiac surgery. To test the hypothesis that commonly used drugs could cause apoptosis of immune cells, the proapoptotic effects of heparin and catecholamines (dopamine and dobutamine) on peripheral blood lymphocytes were evaluated. Peripheral blood lymphocytes were purified from blood samples of normal healthy volunteers. These cells were cultured in the presence of heparin, dobutamine or dopamine. The apoptosis was quantified by Annexin V fluorescent assay, by DNA content and by morphological assessment. Lymphocytes did not show significant levels of apoptosis induction after 24 hours of incubation with heparin. Both dopamine and dobutamine demonstrated a clear apoptosis inducing effect on lymphocytic population after 24 and 48 hours of culture, in concentrations comparable with the clinically used levels. Apoptosis was time and concentration dependent for both catecholamines. The dopamine and dobutamine effect on lymphocyte viability was due, at least partially, to lymphocyte beta receptor engagement, as proved by blocking the receptor with propranolol. These results suggest that catecholamines could induce apoptosis of lymphocytes. This finding may be associated with immunosuppression observed in patients undergoing cardiac surgery.
Cioca
D P
DP
Department of Internal Medicine, Shinshu University School of Medicine, Nagano, Japan.
Watanabe
N
N
Isobe
M
M
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D006348:Cardiac Surgical Procedures; D002395:Catecholamines / Q000494:pharmacology*; D002470:Cell Survival; D004280:Dobutamine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D008214:Lymphocytes / Q000166:cytology*; D008297:Male
D002395:Catecholamines; D004280:Dobutamine; D006493:Heparin; D004298:Dopamine