Transient cyclic AMP accumulation during antibody-dependent cytotoxicity mediated by monocytes and neutrophils.

Monocyte and neutrophil cyclic nucleotide levels were recorded during antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by monocytes and neutrophils. Addition of sensitized group A erythrocytes to monocytes and neutrophils and sensitized Rhesus D erythrocytes to monocytes gave a prompt one and a half to two-fold increase in cAMP levels (with maximal increases after 5–15 sec). No change in cGMP was obtained. In contrast to monocytes no cAMP increment was observed in neutrophils after addition of sensitized Rhesus D erythrocytes compared with the fact that monocytes, but not neutrophils, are effector cells within the Rhesus test system. In normal phagocytes the cAMP response during ADCC was only observed whenever cytolysis took place and was easily avoided by treating the erythrocytes with normal AB serum or diluted specific antibody. The cAMP levels were again decreasing before the cytotoxic process (erythrolysis, activation of hexose monophosphate shunt and lysosomal enzyme release) could significantly be observed. The increments of cAMP may therefore be one of the earliest metabolic events resulting from the binding of IgG-coated erythrocytes to the phagocyte Fc-receptors. Patients with chronic granulomatous disease (CGD) and carriers of the X-linked disease had severely depressed ADCC. However, the initiation of ADCC gave a cAMP increase not different from normals. As monocytes and neutrophils from patients with CGD cannot produce reduced oxygen radicals the cAMP increment observed during ADCC may therefore be unrelated to the respiratory burst of ADCC.