Monocytes activate eosinophils for enhanced helminthotoxicity and increased generation of leukotriene C4

Abstract

ACKNOWLEDGEMENTS We would like to thank Dr Irmeli Penttila for reading the manuscript and Drs 10hn David and K. Frank Austen for helpful advice and discussion during the course of these studies.Recent observations have shown that eosinophils are activated in certain clinical conditions and that activation may enhance the role of eosinophils in immune protection against helminth parasites and in the pathogenesis of certain diseases associated with high eosinophilia. Our laboratory has attempted to identify the immunological mechanisms causing such an activation. The data summarized here show that eosinophils can be activated in vitro with supernatants of resting or stimulated monocytes. The supernatants enhance eosinophil helminthotoxicity by increasing cell degranulation; they also enhance the generation of leukotrienes in eosinophils by exerting a permissive effect on an early step of arachidonic acid metabolism. Biochemical analysis of the enhancing activities suggests that they are carried by a unique molecule or a unique set of molecules whose biochemical and functional properties are different from those of previously described monokines such as IL-1, IFN-??,??, CSF and TNF. Studies on individuals with chronic schistosomiasis suggest that such regulatory interactions between eosinophils and macrophages may take place in the hepatic granulomatous reactions in patients with hepatosplenic schistosomiasis