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Updated: Mar 13, 2026
Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
Phagocytosis of bone marrow derived macrophages is controlled by phosphoinositide 3-kinase γ
Anne Kresinsky1, Nadine Schneble1, Caroline Schmidt1
1Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
Abstract:
Due to their ability to phagocytise invading microbes macrophages play a key role in the innate and acquired immune system. In this article the role of phosphoinositide 3-kinase gamma (PI3Kγ) for phagocytosis was studied in bone marrow derived macrophages (BMDM). By using genetic and pharmacological approaches our data clearly demonstrate PI3Kγ is acting as a mediator of macrophage phagocytosis. Phagocytosis of LPS activated BMDM was reduced in PI3Kγ depleted primary BMDM or macrophage cell line J774. Depletion of other class I phosphoinositide 3-kinases did not alter phagocytic activity. Partial reduction of the phagocytic index of BMDM expressing kinase inactive PI3Kγ indicate a lipid-kinase independent role of the PI3Kγ protein. Since inhibition of PI3Kγ interaction partner phosphodiesterase PDE3B reduced BMDM phagocytosis and PI3Kγ knock out super stimulated cAMP level, our data reveal that PI3Kγ protein mediated suppression of cAMP signalling is a critical for efficient phagocytosis of macrophages.
Insights
Phosphoinositide 3-kinase gamma (PI3Kγ) is crucial for macrophage phagocytosis. This study reveals PI3Kγ suppresses cAMP signaling, which is essential for efficient microbial engulfment by macrophages.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophages are key immune cells involved in phagocytosis.
- Phosphoinositide 3-kinases (PI3Ks) are critical regulators of cellular processes.
Purpose of the Study:
- To investigate the role of phosphoinositide 3-kinase gamma (PI3Kγ) in macrophage phagocytosis.
- To elucidate the mechanism by which PI3Kγ influences phagocytic activity.
Main Methods:
- Genetic depletion of PI3Kγ in bone marrow-derived macrophages (BMDM) and J774 cell line.
- Pharmacological inhibition of PI3Kγ and its interaction partner PDE3B.
- Analysis of phagocytic activity and cAMP levels.
Main Results:
- PI3Kγ depletion significantly reduced macrophage phagocytosis.
- Other class I PI3Ks depletion did not affect phagocytic activity.
- PI3Kγ kinase-inactive mutants showed reduced phagocytosis, suggesting a lipid-kinase independent role.
- Inhibition of PDE3B and PI3Kγ knockout led to increased cAMP levels, impairing phagocytosis.
Conclusions:
- PI3Kγ acts as a critical mediator of macrophage phagocytosis.
- PI3Kγ's role in phagocytosis is partly independent of its lipid-kinase activity.
- PI3Kγ-mediated suppression of cAMP signaling is essential for efficient macrophage phagocytosis.
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