CHEMOATTRACTANT-INDUCED NADPH OXIDASE ACTIVITY IN HUMAN MONOCYTES IS TERMINATED WITHOUT ANY ASSOCIATION OF RECEPTOR-LIGAND COMPLEX TO CYTOSKELETON

When the chemotactic peptide formylmethionyl-leucyl-phenylalanine bind s to its cell surface receptor, a transmembrane signal is generated th at activates the superoxide-producing NADPH oxidase of human phagocyte s. Comparing monocytes and neutrophils with regard to the production o f superoxide anion induced by the peptide, we found a similar time-cou rse for both types of cells. In neutrophils, ligand binding induced a conversion of the receptor to a high-affinity form, a change suggested to be due to an association of the receptor-ligand complex to the Tri ton X-100-insoluble cytoskeleton. This event has been hypothesized to terminate the signal that activates the NADPH oxidase and thereby resu lts in cessation of the cellular production of superoxide anion. Neutr ophils preincubated with the cytoskeleton-disrupting drug cytochalasin B showed an increased and prolonged superoxide anion production after activation with the peptide, thus indicating that the cytoskeleton is involved in terminating this response. Formylmethionyl-leucylphenylal anine was also found to induce polymerization of actin in monocytes; h owever, cytochalasin B had no effect on the peptide-induced generation of superoxide anion in these cells. Furthermore, also in monocytes, l igand binding induced a conversion of the receptor to a high-affinity form; however, the receptor-ligand complex did not coisolate with the Triton X-100-insoluble cytoskeleton. These results indicate that, in m onocytes, the NADPH oxidase activating pathway is terminated without a ny association of the receptor-ligand complex to the Triton X-100-inso luble cytoskeleton.