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A selective defect in tissue factor mRNA expression in monocytes from AIDS patients
J L Lathey1, J M Agosti, J A Nelson
1Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Abstract:
Expression of tumor necrosis factor (TNF alpha), tissue factor (TF), and interleukin 1-beta (IL-1 beta) mRNA was evaluated in monocytes isolated from patients infected with human immunodeficiency virus (HIV). There was a significant depression (66%) of the induced level of TF mRNA expression in response to lipopolysaccharide. Conversely, the response of TNF alpha and IL-1 beta, following LPS induction, was "normal." TF mRNA reduction was also observed to a lesser degree in AIDS-related complex patients (20%) but not in asymptomatic seropositives. TF is necessary for initiation of the coagulation protease cascade, leading to thrombin production and fibrin deposition, which play a role in inflammatory responses. Its selective reduction may be a factor in the diminished resistance to secondary infections observed in AIDS. Further, since the TF defect increases as patients progress toward AIDS, it may serve as a marker for disease progression.
Insights
Human immunodeficiency virus (HIV) infection significantly reduces tissue factor (TF) mRNA expression in monocytes. This defect worsens with disease progression, potentially impacting secondary infections and serving as an AIDS progression marker.
Area of Science:
- Immunology
- Hematology
- Virology
Background:
- Monocytes play a crucial role in immune responses and coagulation.
- Human immunodeficiency virus (HIV) infection is associated with immune dysregulation and increased susceptibility to infections.
- Tissue Factor (TF) initiates the coagulation cascade, influencing inflammation and fibrin deposition.
Purpose of the Study:
- To investigate the expression of mRNA for tumor necrosis factor-alpha (TNF alpha), tissue factor (TF), and interleukin-1 beta (IL-1 beta) in monocytes from HIV-infected patients.
- To determine if TF mRNA expression levels correlate with HIV disease progression.
Main Methods:
- Monocytes were isolated from patients with HIV infection, AIDS-related complex, and asymptomatic seropositive individuals.
- Lipopolysaccharide (LPS) was used to induce the expression of TNF alpha, TF, and IL-1 beta mRNA.
- Quantitative analysis of specific mRNA levels was performed.
Main Results:
- A significant 66% reduction in LPS-induced TF mRNA expression was observed in HIV patients.
- TNF alpha and IL-1 beta mRNA responses to LPS were normal in HIV patients.
- A lesser reduction (20%) in TF mRNA was noted in AIDS-related complex patients, with no reduction in asymptomatic seropositives.
Conclusions:
- Selective depression of TF mRNA expression in HIV infection may contribute to diminished resistance to secondary infections.
- The progressive reduction of TF mRNA as HIV advances suggests its potential as a marker for disease progression.
- Understanding TF dysregulation in HIV is crucial for managing coagulation and immune complications.