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Impairment of polymorphonuclear neutrophil function in HIV-infected patients
C Elbim1, M H Prevot, F Bouscarat
1INSERM U294, Paris, France.
Abstract:
Impaired polymorphonuclear neutrophil (PMN) function may contribute to the onset of certain bacterial and fungal infections and to tissue damage in human immunodeficiency virus (HIV)-infected patients. Published data on PMN function in HIV infection are controversial, possibly because most studies have involved PMNs isolated from the normal blood environment by various procedures that may modify PMN responses. We therefore used flow cytometry to study the expression of adhesion molecules at the PMN surface, actin polymerization, and the oxidative burst of whole-blood PMNs in 42 HIV-infected patients at different stages of the disease. These PMNs were activated in vivo, as shown by increased expression of the adhesion molecule CD11b/CD18, reduced L-selectin antigen expression, increased actin polymerization, and increased H2O2 production. The alterations were present in asymptomatic patients with CD4+ cell counts above 500/microliters and did not increase with progression of the disease. This PMN activation could contribute to the oxidative stress described in HIV infection. Stimulation by bacterial N-formyl peptides showed dysregulation of L-selectin shedding and decreased H2O2 production after cx vivo priming with tumor necrosis factor-alpha or interleukin-8. These latter impairments, which correlated with the decrease in CD4+ lymphocyte numbers, could contribute to the increased susceptibility of HIV-infected patients to bacterial infections.
Insights
Polymorphonuclear neutrophil (PMN) function in HIV patients shows in vivo activation, potentially contributing to oxidative stress. However, impaired responses to bacterial stimuli suggest increased susceptibility to infections.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Polymorphonuclear neutrophil (PMN) dysfunction is implicated in infections and tissue damage in human immunodeficiency virus (HIV)-infected individuals.
- Previous studies on PMN function in HIV are conflicting, possibly due to ex vivo isolation methods altering cellular responses.
Purpose of the Study:
- To investigate PMN function in whole blood from HIV-infected patients using flow cytometry.
- To assess surface molecule expression, actin polymerization, and oxidative burst in PMNs across different HIV disease stages.
Main Methods:
- Flow cytometry analysis of whole-blood PMNs from 42 HIV-infected patients.
- Measurement of CD11b/CD18 and L-selectin expression, actin polymerization, and hydrogen peroxide (H2O2) production.
- Assessment of PMN responses to bacterial N-formyl peptides after ex vivo priming.
Main Results:
- In vivo activation of PMNs observed in HIV patients, indicated by increased CD11b/CD18, reduced L-selectin, enhanced actin polymerization, and increased H2O2 production.
- These alterations were present even in asymptomatic patients and did not worsen with disease progression.
- Impaired L-selectin shedding and reduced H2O2 production upon stimulation were noted, correlating with lower CD4+ lymphocyte counts.
Conclusions:
- PMNs in HIV-infected patients exhibit in vivo activation, potentially contributing to oxidative stress.
- Despite in vivo activation, PMNs show impaired responses to certain stimuli, suggesting a potential mechanism for increased susceptibility to bacterial infections in advanced HIV.
- The findings highlight the complex alterations in PMN function during HIV infection and their clinical implications.