HUMAN NEUTROPHIL AND MACROPHAGE CHEMOKINESIS INDUCED BY CARDIOPULMONARY BYPASS - LOSS OF DAME AND IL-1 CHEMOTAXIS

Cardiopulmonary bypass (CPB) induces both cellular immunosuppression and an inflammatory response. In an effort to better characterize CPB-induced immune dysfuntion, we examined the chemotaxic ability of human granulocytes and macrophages to D-Ala2-Met-enkephalin (DAME) and interleukin (IL)-1alpha with computer-assisted microscopic image analysis before, during and after CPB. Spontaneous granulocyte and macrophage activation increased from 6% and 8% (before) to 52% and 44% (during) and then 39% and 31% after (38 h) CPB, respectively. These activated cells, characterized by conformational changes and locomotion, exhibited chemokinesis. Furthermore, no direct response to either DAME or IL-1alpha was observed in the bypass and postoperative specimens. Cellular velocity was 0.14 and 0.07 mum s-1 for control spontaneously activated granulocytes and macrophages, respectively, and equal to the velocity observed for DAME and IL-1alpha exposed cells, during and after CPB. CPB-unexposed cells, influenced only by the chemotaxic agents, exhibited a 3-4-fold increase in their velocity. Additionally, the migratory path of the activated cells obtained during and after CPB exhibited chemokinesis, rather than chemotaxis, when placed in a concentration gradient of either signal molecule. Cells exposed to fentanyl, the anesthetic agent, exhibited the same behavior as controls, as did those treated with morphine sulphate. However, at higher concentrations (greater-than-or-equal-to 10 ng ml-1) fentanyl and morphine reduced granulocyte and macrophage activity, demonstrating that CPB caused the opposite effect of fentanyl and also that CPB exposure overcame the pharmacological inhibitory effect of the mu opiate ligands. Based on these results, we surmise that both granulocytes and macrophages exposed to CPB were dysfunctional, despite their relative activated state, since they did not respond to chemotaxic agents. The results thus constitute further evidence that CPB induces a profound immunocyte dysfunctional state.