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Cytokine regulation of endocytic activity in primary human macrophages was studied to define ultrastructural changes and mechanisms of pinocytic regulation associated with cytokines secreted by activated T cells. The effects of IFN-gamma (type 1) and IL-4/IL-13 and IL-10 (type 2) cytokines on fluid phase and mannose receptor-mediated endocytosis were assessed by horseradish peroxidase and colloidal gold-BSA uptake and computer-assisted morphometric analysis. IL-4 and IL-13 enhanced fluid phase pinocytosis and mannose receptor-mediated uptake by activation of phosphatidylinositol 3-kinase. Inhibition of actin assembly showed that both cytokines exerted actin-dependent and -independent effects. Ultrastructurally, IL-4 and IL-13 increased tubular vesicle formation underneath the plasma membrane and at pericentriolar sites, concurrent with decreased particle sorting to lysosomes. By contrast, IL-10 or IFN-gamma decreased both fluid phase pinocytosis and mannose receptor-mediated uptake. IFN-gamma stimulated increased particle sorting to perinuclear lysosomes, while IL-10 decreased this activity. In summary, our data document differential effects on macrophage endocytic functions by type 1 or type 2 cytokines associated with induction and effector pathways in immunity.


Journal article


J Immunol

Publication Date





4606 - 4613


Actins, Cell Nucleus, Endocytosis, Endosomes, Gold Colloid, Golgi Apparatus, Horseradish Peroxidase, Humans, Interferon-gamma, Interleukin-10, Interleukin-13, Interleukin-4, Lectins, C-Type, Lysosomes, Macrophage Activation, Macrophages, Mannose-Binding Lectins, Phosphatidylinositol 3-Kinases, Receptors, Cell Surface, Th1 Cells, Th2 Cells