Type 1 and type 2 cytokine regulation of macrophage endocytosis: differential activation by IL-4/IL-13 as opposed to IFN-gamma or IL-10.
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.
Montaner
L J
LJ
The Wistar Institute, Philadelphia, PA 19104, USA. montaner@wistar.upenn.edu
da Silva
R P
RP
Sun
J
J
Sutterwala
S
S
Hollinshead
M
M
Vaux
D
D
Gordon
S
S
D000199:Actins / Q000378:metabolism / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000276:immunology*; D011992:Endosomes / Q000201:enzymology / Q000648:ultrastructure; D017979:Gold Colloid; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000502:physiology*; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D037181:Lectins, C-Type; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
D000199:Actins; D017979:Gold Colloid; D006735:Horseradish Peroxidase; D007371:Interferon-gamma; D016753:Interleukin-10; D018793:Interleukin-13; D015847:Interleukin-4; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D019869:Phosphatidylinositol 3-Kinases; D011956:Receptors, Cell Surface