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Cytokine production by rabbit alveolar macrophages: differences between activated and suppressor cell phenotypes
H Kobayashi1, M Kobayashi, T A Heming
1Department of Internal Medicine, The University of Texas Medical Branch, Galveston 77555-0835, USA.
Abstract:
The differences between cytokine-producing profiles of activated macrophages (A-M phi) and suppressor macrophages (S-M phi) were examined. A-M phi, which exhibited cytotoxicity against RK-13 cells, were generated from resident rabbit alveolar M phi by treatment with lymphokine solution (culture fluids of rabbit spleen cells stimulated with concanavalin A [Con A]). S-M phi, which were able to inhibit cellular proliferations of rabbit spleen cells stimulated with Con A, were generated from resident alveolar M phi by treatment with 1-methyladenosine (an immunosuppressive molecule in tumourous ascites fluids). When A-M phi were stimulated with lipopolysaccharide (LPS) in vitro, the cells produced significantly more interleukin (IL)-1 (approximately 1.4 times), IL-6 (approximately 2.1 times), IL-12 (approximately 60 times), and tumour necrosis factor-alpha (TNF-alpha) (approximately 37 times) than did resting macrophages (R-M phi) stimulated with LPS as control cells. After the stimulation with LPS, both A-M phi and R-M phi did not produce transforming growth factor-beta (TGF-beta). In contrast, when S-M phi were stimulated with LPS in vitro, the cells produced significantly more TGF-beta (approximately 1.6 times) and significantly less IL-6 (approximately 1.8 times) than did control cells. Also, S-M phi did not produce IL-1, IL-12, and TNF-alpha into their culture fluids after the stimulation with LPS. These results show the differences between cytokine-producing profiles of A-M phi and S-M phi, and characteristics of their cytokine-producing profiles are analogous to T cell subsets. Differences displayed in the cytokine profiles may contribute to the effector (A-M phi) or the suppressor (S-M phi) functions of alveolar M phi.
Insights
Activated macrophages (A-M phi) produce high levels of pro-inflammatory cytokines, while suppressor macrophages (S-M phi) produce TGF-beta. These distinct cytokine profiles influence macrophage function, analogous to T cell subsets.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages play critical roles in immune responses.
- Distinct macrophage subsets, such as activated (A-M phi) and suppressor (S-M phi) macrophages, exhibit different functional properties.
- Understanding macrophage cytokine production is key to elucidating immune regulation.
Purpose of the Study:
- To investigate and compare the cytokine-producing profiles of activated macrophages (A-M phi) and suppressor macrophages (S-M phi).
- To determine the functional implications of these distinct cytokine profiles in macrophage effector and suppressor functions.
Main Methods:
- Resident rabbit alveolar macrophages were differentiated into A-M phi using lymphokine solution and S-M phi using 1-methyladenosine.
- Cytokine production (IL-1, IL-6, IL-12, TNF-alpha, TGF-beta) was analyzed in A-M phi, S-M phi, and resting macrophages (R-M phi) after lipopolysaccharide (LPS) stimulation in vitro.
Main Results:
- A-M phi produced significantly higher levels of IL-1, IL-6, IL-12, and TNF-alpha compared to R-M phi after LPS stimulation.
- S-M phi produced significantly higher levels of TGF-beta and lower levels of IL-6 than control cells after LPS stimulation.
- S-M phi did not produce IL-1, IL-12, or TNF-alpha, while both A-M phi and R-M phi did not produce TGF-beta after LPS stimulation.
Conclusions:
- Activated and suppressor macrophages exhibit distinct and opposing cytokine-producing profiles.
- The observed cytokine profiles of A-M phi and S-M phi are analogous to T helper cell subsets.
- These differences in cytokine production likely contribute to the effector functions of A-M phi and the suppressor functions of S-M phi.