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Updated: Jun 16, 2026
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
5-Lipoxygenase metabolism in alveolar macrophages from subjects infected with the human immunodeficiency virus
M J Coffey1, S M Phare, P H Kazanjian
1Division of Pulmonary Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA.
Abstract:
Pulmonary infection represents a major source of morbidity and mortality in AIDS. One important component of pulmonary host defense is the elaboration by resident alveolar macrophages (AM) of proinflammatory leukotrienes (LT) and other 5-lipoxygenase (5-LO) metabolites of arachidonic acid (AA). In this study, we compared the 5-LO metabolic capacity of AM isolated from normal controls with two groups of HIV-infected subjects: (1) patients with low CD4 counts undergoing diagnostic evaluation for pulmonary indications, and (2) volunteers without pulmonary complaints stratified into normal (> 500) and low (< 200) CD4 count groups. Compared with AM from control subjects, AM from HIV-infected subjects with normal and low CD4 counts demonstrated a marked reduction in LT synthesis. This reduced metabolic capacity could not be attributed to in vivo activation because there was no increase in lavage fluid LTB4 levels. However, there was a reduction (approximately twofold) in 5-LO protein expression in both the normal and the low CD4 subsets. 5-LO-activating protein (FLAP) expression was unchanged in cells from the normal CD4 HIV group, but was decreased threefold in the two groups with low CD4 counts. These observations indicate that there is a graded defect in the 5-LO metabolic capacity of AM from HIV-infected subjects, with decreased expression of only 5-LO in the normal CD4 group, and decreased expression of both 5-LO and FLAP in the low CD4 group. This defect would be expected to compound the immunosuppression seen in these subjects.
Insights
Alveolar macrophages from HIV-infected individuals show reduced leukotriene synthesis, a key part of pulmonary defense. This defect worsens with lower CD4 counts, impacting immune function in AIDS patients.
Area of Science:
- Immunology
- Pulmonology
- Virology
Background:
- Pulmonary infections are a major cause of illness and death in AIDS patients.
- Pulmonary host defense relies on alveolar macrophages (AM) producing leukotrienes (LT) and other 5-lipoxygenase (5-LO) metabolites.
- HIV infection can impair immune responses, potentially affecting AM function.
Purpose of the Study:
- To compare the 5-LO metabolic capacity of AM in normal controls versus HIV-infected individuals with varying CD4 counts.
- To investigate the expression of 5-LO and 5-LO-activating protein (FLAP) in AM from these groups.
- To understand how HIV-related immunosuppression affects AM's role in pulmonary defense.
Main Methods:
- Isolation of alveolar macrophages (AM) from healthy controls and HIV-infected patients (stratified by CD4 counts).
- Measurement of leukotriene (LT) synthesis capacity in AM.
- Assessment of 5-lipoxygenase (5-LO) and 5-LO-activating protein (FLAP) protein expression in AM.
Main Results:
- AM from HIV-infected subjects (both normal and low CD4 counts) showed significantly reduced LT synthesis compared to controls.
- Reduced 5-LO protein expression was observed in AM from both HIV-infected groups.
- Decreased FLAP expression was found in AM from HIV-infected individuals with low CD4 counts (<200).
Conclusions:
- A graded defect in AM 5-LO metabolic capacity exists in HIV-infected individuals, correlating with CD4 count.
- Reduced 5-LO and FLAP expression in AM may impair pulmonary host defense in advanced HIV/AIDS.
- These findings highlight a potential mechanism contributing to increased pulmonary infections in HIV/AIDS.
