Differential ability of proinflammatory and anti-inflammatory macrophages to perform macropinocytosis
| Autor: | Michael Gütschow, Johnathan Canton, Dar’ya S. Redka, Sergio Grinstein |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Lipopolysaccharides
rho GTP-Binding Proteins 0301 basic medicine medicine.drug_class Inflammation Biology Anti-inflammatory Proinflammatory cytokine Cell membrane Phosphatidylinositol 3-Kinases 03 medical and health sciences medicine Humans Receptor Molecular Biology Cells Cultured Macrophages Pinocytosis Cell Membrane Cell Polarity Granulocyte-Macrophage Colony-Stimulating Factor Articles Cell Biology Phenotype Signaling 3. Good health Cell biology 030104 developmental biology Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Cytokines medicine.symptom Receptors Calcium-Sensing Biomarkers medicine.drug |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Although anti-inflammatory macrophages perform macropinocytosis constitutively, proinflammatory macrophages do not, due to impaired signaling of the calcium-sensing receptor. However, macropinocytosis can be elicited in proinflammatory macrophages by agonists that induce the recruitment of phosphatidylinositol 3-kinase to the plasma membrane. 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. |
| Databáze: | OpenAIRE |
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