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or IL-101
*
The Wistar Institute, Philadelphia, PA 19104; and
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
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-
(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- decreased
both fluid phase pinocytosis and mannose receptor-mediated uptake.
IFN- 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.
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