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Updated: May 29, 2026

Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4
Published on: August 21, 2017
Defective macrophage function in aquaporin-3 deficiency
Na Zhu1, Xuechao Feng, Chengyan He
1Central Research Laboratory, Bethune Second Hospital of Jilin University, Changchun, 130041, PR China.
Abstract:
Macrophages play an essential role in innate immunity. We found that mouse resident peritoneal macrophages (mRPMs) express the aquaglyceroporin aquaporin-3 (AQP3) in a plasma membrane pattern. AQP3-deficient (AQP3(-/-)) mice showed significantly greater mortality than wild-type (AQP3(+/+)) mice in a model of bacterial peritonitis. To establish the cellular mechanism of the peritonitis phenotype, measurements were made of mRPM phagocytosis, migration, and water/glycerol permeability. We found significantly impaired engulfment of Escherichia coli and chicken erythrocytes in AQP3(-/-) vs. AQP3(+/+) mRPMs, as well as impaired migration of AQP3(-/-) mRPMs in response to a chemotactic stimulus. In AQP3(+/+) mRPMs, AQP3 was polarized to pseudopodia at the leading edge during migration and around the phagocytic cup during engulfment. Water and glycerol permeabilities in mRPMs from AQP3(-/-) mice were reduced compared to mRPMs from AQP3(+/+) mice. Cellular glycerol and ATP content were remarkably lower in AQP3(-/-) vs. AQP3(+/+) mRPMs, and glycerol supplementation partially rescued the reduced ATP content and impaired function of AQP3(-/-) mRPMs. These data implicate AQP3 as a novel determinant in macrophage immune function by a cellular mechanism involving facilitated water and glycerol transport, and consequent phagocytic and migration activity. This is the first study demonstrating involvement of an aquaporin in innate immunity. Our results suggest AQP3 as a novel therapeutic target in modulating the immune response in various infectious and inflammatory conditions.
Insights
Aquaporin-3 (AQP3) is crucial for macrophage immune function, facilitating water and glycerol transport essential for phagocytosis and migration. AQP3 deficiency impairs these functions, increasing susceptibility to bacterial infections.
Area of Science:
- Immunology
- Cell Biology
- Physiology
Background:
- Macrophages are vital innate immune cells.
- Aquaporins are membrane channels regulating water and small solute transport.
- The role of aquaporins in immune cell function is largely unexplored.
Purpose of the Study:
- To investigate the role of aquaporin-3 (AQP3) in macrophage function and innate immunity.
- To elucidate the cellular mechanisms underlying AQP3's contribution to immune responses.
Main Methods:
- Utilized aquaporin-3 deficient (AQP3(-/-)) and wild-type (AQP3(+/+)) mice.
- Assessed macrophage phagocytosis, migration, and water/glycerol permeability.
- Measured cellular glycerol and ATP content.
- Investigated the effect of glycerol supplementation.
Main Results:
- AQP3(-/-) mice exhibited higher mortality in bacterial peritonitis.
- AQP3 deficiency impaired macrophage phagocytosis of bacteria and erythrocytes.
- Macrophage migration and water/glycerol permeability were reduced in AQP3(-/-) mice.
- Cellular glycerol and ATP levels were lower in AQP3(-/-) macrophages, with glycerol supplementation partially restoring function.
Conclusions:
- AQP3 is a novel determinant of macrophage immune function via facilitated water and glycerol transport.
- AQP3 is essential for macrophage phagocytic and migration activities.
- AQP3 represents a potential therapeutic target for modulating immune responses in infectious and inflammatory conditions.
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