Dithranol-mediated, does-dependent priming and activation of luminol-enhanced chemiluminescence responses of human neutrophils in vitro

Publisher Website
Google Scholar
Abstract
At concentrations of 10 μg/ml and greater, dithranol (anthralin) caused an intense, dose‐related activation of luminol‐enhanced chemiluminescence (LECL) of human neutropils and also increased oxygen consumption by these cells. Activation of LECL, which was maximal with 40 μg/ml dithranol, occurred promptly, peaked at 3–5 min, then declined. Dithranol‐mediated stimulation of LECL was inhibited by catalase and by the protein kinase C inhibitor, H‐7. Neutrophils from individuals with chronic granulomatous disease were unresponsive to the pro‐oxidative effects of dithranol. At concentrations of 2.5 μg/ml and less, dithranol did not directly activate the LECL responses of neutrophils. However pre‐treatment of neutrophils with dithranol at concentrations of 0.5–2.5 μg/ml increased the LECL‐responses of cells subsequently two distinct dose‐related, pro‐oxidative interactions of dithranol with human neutrophils: low‐dose priming and high‐dose activation of oxidant generation. Since phagocyte‐derived reactive oxidants are immunosuppressive, these pro‐oxidative interactions of dithranol with human neutrophils may contribute to the pharmacotherapeutic mechanisms of this agent.