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Antimicrobial properties of Kupffer cells
1Infectious Disease Section, Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Infection and Immunity
|June 1, 1988
Summary
Kupffer cells, liver macrophages, exhibit antimicrobial activity and can be activated by Propionibacterium acnes. Activation enhances their ability to combat pathogens like Toxoplasma gondii.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Kupffer cells are resident liver macrophages crucial for immune surveillance.
- Understanding Kupffer cell antimicrobial functions is vital for liver immunity.
Purpose of the Study:
- To characterize the antimicrobial activities and activation states of Kupffer cells.
- To investigate Kupffer cell responses to microbial stimuli and infections.
Main Methods:
- Isolation of liver macrophages (Kupffer cells) using collagenase and DNase perfusion.
- Assessing Kupffer cell morphology, esterase activity, and phagocytosis of zymosan.
- Evaluating Toxoplasma gondii multiplication within Kupffer cells.
- Stimulating Kupffer cells with heat-killed Propionibacterium acnes (P. acnes) and assessing reactive oxygen intermediate generation via Nitro Blue Tetrazolium reduction.
- Investigating Kupffer cell activation in athymic mice and during parasitic infections (T. gondii, Giardia muris).
- Assessing the effect of gamma interferon on Kupffer cell permissiveness to T. gondii in vitro.
Main Results:
- Isolated Kupffer cells demonstrated typical macrophage characteristics and phagocytic capacity.
- T. gondii multiplied in Kupffer cells, with intermediate replication compared to other macrophage types.
- Intravenous P. acnes injection uniformly activated Kupffer cells, enhancing their capacity to generate reactive oxygen intermediates.
- P. acnes activated Kupffer cells but not spleen macrophages.
- Kupffer cell activation by P. acnes was independent of T cells.
- Kupffer cells were not activated during latent T. gondii or acute Giardia muris infections.
- In vitro, Kupffer cells became permissive to T. gondii, an effect partially inhibited by gamma interferon.
Conclusions:
- Kupffer cells possess inherent antimicrobial functions and can be significantly activated by P. acnes.
- Activated Kupffer cells exhibit enhanced pathogen-killing capabilities, including reactive oxygen intermediate production.
- Kupffer cell activation pathways are distinct from systemic responses and T cell-dependent activation is not required.
- These findings highlight Kupffer cells as key players in liver innate immunity with potential for therapeutic modulation.