Interferon suppresses pinocytosis but stimulates phagocytosis in mouse peritoneal macrophages

Related changes in cytoskeletal organization

E. Wang, J. Michl, Lawrence Pfeffer, S. C. Silverstein, I. Tamm

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Treatment of thioglycolate-elicited macrophages with mouse β-interferon markedly reduces pinocytosis of horseradish peroxidase and fluorescein isothiocyanate (FITC)-dextran but stimulates phagocytosis of IgG-coated sheep erythrocytes. Experiments with FITC-dextran have revealed that the overall decrease in pinocytosis is due to a nearly complete inhibition of pinocytosis in a large fraction of interferon-treated macrophages. In the remaining cells pinocytosis continues at a rate similar to that in untreated control cells. A considerable reduction in the number of cells pinocytosing FITC-dextran was observed within 12 h from the beginning of interferon treatment. Measurement of the overall level of pinocytic activity with horseradish peroxidase showed a progressive decline through 72 h of treatment. In the interferon-sensitive subpopulation, there were marked changes in cytoskeletal organization. Microtubules and 10-nm filaments were aggregated in the perinuclear region while most of the peripheral cytoplasm became devoid of these cytoskeletal structures as observed by fluorescence and electron microscopy. In addition, interferon treatment of macrophages appeared to disrupt the close topological association between bundles of 10-nm filaments and organelles such as mitochondria, lysosomes, and elements of the Golgi apparatus and endoplasmic reticulum. Such alterations in the distribution of microtubules and 10-nm filaments were not seen in the interferon-insensitive subpopulation. We have investigated the mechanism of the interferon-induced enhancement of phagocytic activity by binding IgG-coated sheep erythrocytes to mouse peritoneal macrophages at 4 °C and then initiating a synchronous round of ingestion by warming the cells to 37 °C. Thioglycolate-elicited macrophages that had been treated with mouse β-interferon ingested IgG-coated erythrocytes faster and to a higher level than control cells in a single round of phagocytosis. In interferon-treated cultures, phagocytic cups became evident with 30 s of the shift of cultures from 4 ° to 37 °C, whereas in control cultures, they appeared in 2 min. Cytochalasin D, an inhibitor of actin assembly and polymerization, abolished phagocytic activity in both control and β-interferon-treated macrophages. However, to inhibit phagocytosis completely in thioglycolate-elicited interferon-treated macrophages, twice as much cytochalasin D was required in the treated as in control cultures. Accelerated association of actin filaments with the plasma membrane during engulfment of the erythrocytes appears to be a major factor contributing to the interferon-induced increase in phagocytic rate. Using monoclonal antibody (2,4G2) to the trypsin-resistant FcRII receptors, no difference was detected between control and interferon-treated macrophages in the abundance of cell surface receptors for IgG. In conclusion, the stimulation of phagocytosis by interferon treatment of macrophages appears to reflect increased efficiency of the phagocytic process and may involve alterations of the plasma membrane and associated actin filaments; the suppression of pinocytosis may be due to alterations in these structures as well as to disruption of the extended network of microtubules and 10-nm filaments.

Original languageEnglish (US)
Pages (from-to)1328-1341
Number of pages14
JournalJournal of Cell Biology
Volume98
Issue number4
DOIs
StatePublished - Jan 1 1984
Externally publishedYes

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Pinocytosis
Peritoneal Macrophages
Phagocytosis
Interferons
Macrophages
Thioglycolates
Immunoglobulin G
Erythrocytes
Microtubules
Cytochalasin D
Horseradish Peroxidase
Actin Cytoskeleton
Sheep
Cell Membrane
Cell Surface Receptors
Golgi Apparatus
Lysosomes
Fluorescence Microscopy

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Interferon suppresses pinocytosis but stimulates phagocytosis in mouse peritoneal macrophages : Related changes in cytoskeletal organization. / Wang, E.; Michl, J.; Pfeffer, Lawrence; Silverstein, S. C.; Tamm, I.

In: Journal of Cell Biology, Vol. 98, No. 4, 01.01.1984, p. 1328-1341.

Research output: Contribution to journalArticle

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