Cited by 58Cellular transport and secretionImmune cells in cancerPhagocytosis and Immune Regulation

Differential ability of proinflammatory and anti-inflammatory macrophages to perform macropinocytosis

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Redka, Dar’ya S., Gütschow, Michael, Grinstein, Sergio, Canton, Johnathan·2018·Molecular Biology of the Cell

Abstract

Macropinocytosis mediates the uptake of antigens and of nutrients that dictate the regulation of cell growth by mechanistic target of rapamycin complex 1 (mTORC1). Because these functions differ in proinflammatory and anti-inflammatory macrophages, we compared the macropinocytic ability of two extreme polarization states. We found that anti-inflammatory macrophages perform vigorous macropinocytosis constitutively, while proinflammatory cells are virtually inactive. The total cellular content of Rho-family GTPases was higher in anti-inflammatory cells, but this disparity failed to account for the differential macropinocytic activity. Instead, reduced activity of Rac/RhoG was responsible for the deficient macropinocytosis of proinflammatory macrophages, as suggested by the stimulatory effects of heterologously expressed guanine nucleotide-exchange factors or of constitutively active (but not wild-type) forms of these GTPases. Similarly, differences in the activation state of phosphatidylinositol 3-kinase (PtdIns3K) correlated with the macropinocytic activity of pro- and anti-inflammatory macrophages. Differences in PtdIns3K and Rho-GTPase activity were attributable to the activity of calcium-sensing receptors (CaSRs), which appear to be functional only in anti-inflammatory cells. However, agonists of PtdIns3K, including cytokines, chemokines, and LPS, induced macropinocytosis in proinflammatory cells. Our findings revealed a striking difference in the macropinocytic ability of pro- and anti-inflammatory macrophages that correlates with their antigen-presenting and metabolic activity.

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Crossref · 10.1091/mbc.e17-06-0419

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  • Cytokine CXCL12 and components of bacterial cell wall such as LPS can stimulate macropinocytosis.

    “Moreover, cytokine C-X-C chemokine motif ligand-12 and components of the bacterial cell wall such as lipopolysaccharide (LPS) can stimulate macropinocytosis process [35].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [35]

    The Results section reports that acute LPS treatment markedly stimulated macropinocytosis in both macrophage culture conditions. It also reports stimulation by the chemokines CCL7 and CCL19, but does not identify CXCL12 as a stimulant. No page number is available in our copy. (LLM, conf=0.89)

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Research works printed but not linked: 2

  1. Cassatella MA Bazzoni F Flynn RM Dusi S Trinchieri G Rossi F Molecular basis of interferon-γ and lipopolysaccharide enhancement of phagocyte respiratory burst capability J Biol Chem 1990 265 20241 20246 2173701
  2. West MA Distinct endocytotic pathways in epidermal growth factor-stimulated human carcinoma A431 cells J Cell Biol 1989 109 2731 2739 2556406 PMC2115909

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Authors
Redka, D. S., Gütschow, M., Grinstein, S., & Canton, J.
Affiliations
  • Hospital for Sick Children (CA)
  • University of Bonn (DE)
  • St. Michael's Hospital (CA)
Corresponding author
Grinstein, Sergio
Venue
Molecular Biology of the Cell
Published
2018-01
Volume
29
Issue
1
Pages
53-65
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
OpenAlex
W2766771070
Cited by
58
References
61
Citations by year
2026: 3 · 2025: 8 · 2024: 8 · 2023: 5 · 2022: 11 · 2021: 8 · 2020: 8 · 2019: 1 · 2018: 4 · 2017: 1
FWCI
2.04
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (FOR 2372)
  • Hospital for Sick Children
  • University of North Carolina at Chapel Hill
  • Canadian Institutes of Health Research (FDN143202)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
macropinocytosis, macrophage polarization, inflammatory macrophages, anti-inflammatory macrophages, mTORC1, Rho GTPases, Rac, RhoG, guanine nucleotide exchange factor, phosphatidylinositol 3-kinase, calcium-sensing receptor, antigen uptake, macrophage metabolism, antigen presentation
MeSH terms
Cell Membrane, Cells, Cultured, Humans, Inflammation, Lipopolysaccharides, Macrophages, Phenotype, Pinocytosis, Biomarkers, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Cell Polarity, Phosphatidylinositol 3-Kinases, rho GTP-Binding Proteins, Receptors, Calcium-Sensing

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