Related Experiment Videos
Regulation of 5-lipoxygenase metabolism in mononuclear phagocytes by CD4 T lymphocytes
M J Coffey1, S M Phare, M Peters-Golden
1Division of Pulmonary, University of Michigan Medical Center, Ann Arbor 48109-0642, USA. mcoffey@umich.edu
Abstract:
Alveolar macrophages (AM) are the primary resident effector cells in the alveolus. Leukotrienes (LT) are secreted by AM in their role as defender of the lung. 5-Lipoxygenase (5-LO) catalyzes the synthesis of LT in association with 5-LO-activating protein, termed "FLAP." AM demonstrate increased 5-LO metabolism compared to peripheral blood monocytes (PBM). Activated lymphocytes release mediators which upregulate 5-LO metabolism in PBM. The lymphocyte population of the lung consists predominantly of CD4+ helper constitutively "activated" T cells. We hypothesized that mediators released by pulmonary CD4+ T cells may upregulate and maintain of 5-LO metabolism in PBM as they enter the alveolar space and differentiate into AM. 5-LO metabolism in AM from CD4-depleted mice demonstrated reduced LT synthesis (LTC4: 66.9 +/- 8%; LTB4 61.4 +/- 6.2% control). The decrease in 5-LO metabolism was associated with reduced FLAP (30.1 +/- 14.5% of control) and 5-LO expression (49 +/- 13.7% of control). This defect in AM 5-LO metabolism in CD4-depleted mice was further associated with reduced LTC4 levels in bronchoalveolar lavage (BAL) fluid. In summary, factors secreted constitutively by lung lymphocytes, in particular CD4 cells, contribute to the increased 5-LO metabolism in AM.
Insights
Lung CD4+ T cells influence immune defense by regulating leukotriene (LT) synthesis in alveolar macrophages (AM). Depleting these T cells reduces LT production, impacting lung immunity.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Alveolar macrophages (AM) are key lung effector cells.
- Leukotrienes (LT), synthesized via 5-Lipoxygenase (5-LO) and FLAP, are crucial for lung defense.
- AM exhibit higher 5-LO metabolism than peripheral blood monocytes (PBM).
Purpose of the Study:
- To investigate if CD4+ T cells regulate 5-LO metabolism in AM.
- To determine the role of pulmonary CD4+ T cells in maintaining AM function.
Main Methods:
- CD4+ T cell depletion in mice.
- Measurement of leukotriene synthesis (LTC4, LTB4) in AM.
- Quantification of 5-LO and FLAP expression in AM.
- Analysis of bronchoalveolar lavage (BAL) fluid.
Main Results:
- CD4-depleted mice showed significantly reduced LT synthesis in AM.
- 5-LO and FLAP expression were decreased in AM from CD4-depleted mice.
- Reduced LTC4 levels were observed in the BAL fluid of CD4-depleted mice.
Conclusions:
- Constitutive factors from lung CD4+ T cells enhance 5-LO metabolism in AM.
- CD4+ T cells play a critical role in regulating macrophage-mediated immune responses in the lung.