Differential ability of proinflammatory and anti-inflammatory macrophages to perform macropinocytosis
Open accessAbstract
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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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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The Role of Antigen Presentation in Tumor-Associated Macrophages
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Mannose receptor (MRC1) mediates uptake of dextran by bone marrow–derived macrophages
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CLEC receptors, endocytosis and calcium signaling
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Mannose receptor (MRC1) mediates uptake of dextran in macrophages via receptor-mediated endocytosisPreprint
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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
- PMC
- PMC5746066
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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