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[Histamine produced by macrophage and T lymphocyte: a new type of signal transducer]
1Nagoya University Bioscience Center, Chikusa, Nagoya 464-8601, Japan.
Abstract:
Macrophages (M phi) produce histamine (Hm) when activated by bacterial endotoxin (LPS) through induced histidine decarboxylase (HDC). Among the cytokines tested, GM-CSF or IL-3 specifically augmented the LPS-dependent HDC induction by M phi. Hm formed by M phi regulates synthesis of cytokines such as IL-1, IL-6, G-CSF and M-CSF by the cells per se and may modulate immune reactions and division and differentiation of various hematopoietic cells. Kupffer cells, M phi-like cells in the liver, also synthesize Hm in mice injected with hepatotoxins such as tetradecanoylphorbol acetate or LPS. Hm thus produced by Kupffer cells may participate in the regeneration of the injured liver through induction of hepatocyte growth factor. Concanavalin A (Con A) enhanced Hm formation by T lymphocytes. GM-CSF or IL-3 also enhanced the Hm synthesis by CD4+ and CD8+ T cells. Hm formed by T cells regulates immune reactions such as lymphocyte blastogenesis. In animals infected with gram(-) bacteria Hm is produced by the M phi-T cell system and may regulate immune competence to the bacteria. In addition, Hm may act as a signal transducer between the peripheral immune system and hypothalamus-pituitary-adrenal system, leading to GC secretion, in order to prevent occurrence of tissue injury caused by excess immune reactions.
Insights
Macrophages and T cells produce histamine, a molecule that modulates immune responses and tissue repair. Cytokines like GM-CSF and IL-3 enhance this histamine production, impacting immune cell activity and regeneration.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophages (M phi) and T lymphocytes are key immune cells involved in host defense and tissue homeostasis.
- Histamine (Hm) is a biogenic amine traditionally known for its role in allergic reactions.
- The production and function of histamine by immune cells beyond mast cells are less understood.
Purpose of the Study:
- To investigate the production of histamine by macrophages and T cells.
- To identify factors that regulate histamine synthesis in these immune cells.
- To explore the functional implications of histamine produced by macrophages and T cells in immune responses and tissue repair.
Main Methods:
- Activation of macrophages with bacterial endotoxin (LPS) and assessment of histidine decarboxylase (HDC) activity and histamine production.
- Treatment of T lymphocytes with Concanavalin A (Con A) and analysis of histamine synthesis.
- Investigation of the effects of cytokines, including GM-CSF and IL-3, on histamine production by macrophages and T cells.
- Evaluation of histamine's role in regulating cytokine synthesis and cell differentiation.
Main Results:
- Macrophages produce histamine upon LPS activation, mediated by induced HDC.
- GM-CSF or IL-3 specifically augmented LPS-dependent HDC induction in macrophages.
- Kupffer cells (liver macrophages) synthesize histamine in response to hepatotoxins or LPS, potentially aiding liver regeneration.
- T lymphocytes, stimulated by Con A, also produce histamine, with GM-CSF and IL-3 enhancing this synthesis.
- Histamine produced by macrophages regulates cytokines (IL-1, IL-6, G-CSF, M-CSF) and hematopoietic cell differentiation.
- Histamine from T cells modulates immune reactions like lymphocyte blastogenesis.
- The macrophage-T cell system produces histamine during bacterial infections, potentially regulating immune competence.
- Histamine may signal between the immune system and the HPA axis, influencing glucocorticoid secretion to prevent immune-mediated tissue injury.
Conclusions:
- Macrophages and T cells are significant sources of histamine, contributing to immune regulation and tissue repair.
- Cytokines like GM-CSF and IL-3 play a crucial role in enhancing histamine production by immune cells.
- Histamine produced by these cells influences a range of biological processes, including cytokine synthesis, cell differentiation, and immune responses.
- Histamine acts as a critical mediator in the interplay between the immune system, tissue regeneration, and neuroendocrine pathways.