Neutrophil migration induced by IL-1beta depends upon LTB4 released by macrophages and upon TNF-alpha and IL-1beta released by mast cells

Abstract

In the present study, we investigate whether mast cells and macrophages are involved in the control of IL-1beta-induced neutrophil migration, as well as the participation of chemotactic mediators. IL-1beta induced a dose-dependent neutrophil migration to the peritoneal cavity of rats which depends on LTB(4), PAF and cytokines, since the animal treatment with inhibitors of these mediators (MK 886, PCA 4248 and dexamethasone respectively) inhibited IL-1beta-induced neutrophil migration. The neutrophil migration induced by IL-1beta is dependent on mast cells and macrophages, since depletion of mast cells reduced the process whereas the increase of macrophage population enhanced the migration. Moreover, mast cells or macrophages stimulated with IL-1beta released a neutrophil chemotactic factor, which mimicked the neutrophil migration induced by IL-1beta. The chemotactic activity of the supernatant of IL-1beta-stimulated macrophages is due to the presence of LTB(4), since MK 886 inhibited its release. Moreover, the chemotactic activity of IL-1beta-stimulated mast cells supernatant is due to the presence of IL-1beta and TNF-alpha, since antibodies against these cytokines inhibited its activity. Furthermore, significant amounts of these cytokines were detected in the supernatant. In conclusion, our results suggest that neutrophil migration induced by IL-1beta depends upon LTB(4) released by macrophages and upon IL-1beta and TNFalpha released by mast cells.