Polymorphonuclear neutrophils from human immunodeficiency virus-infected patients show enhanced activation, diminished fMLP-induced L-selectin shedding, and an impaired oxidative burst after cytokine priming.
Impaired polymorphonuclear neutrophil (PMN) function may contribute to the onset of certain life-threatening bacterial and fungal infections in human immunodeficiency virus (HIV)-infected patients. Published data on PMN functional activity in HIV infection are controversial, possibly because most studies have involved PMNs isolated from their blood environment by means of various procedures that may differently affect surface receptor expression and thereby alter cellular 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 polymorphonuclear neutrophils in 42 HIV-infected patients at different stages of the disease. These PMNs were activated in vivo, as demonstrated 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 greater than 500/microL and did not increase with the progression of the disease. Stimulation by bacterial N-formyl peptides showed dysregulation of L-selectin shedding and decreased H2O2 production after ex vivo priming with tumor necrosis factor alpha or interleukin-8 (IL-8). These latter impairments, which correlated with the decrease in CD4+ lymphocyte numbers and with IL-8 and IL-6 plasma levels, could contribute to the increased susceptibility of HIV-infected patients to bacterial infections.
Elbim
C
C
INSERM U294, Paris, France.
Prevot
M H
MH
Bouscarat
F
F
Franzini
E
E
Chollet-Martin
S
S
Hakim
J
J
Gougerot-Pocidalo
M A
MA
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000199:Actins / Q000097:blood; D000328:Adult; D018791:CD4 Lymphocyte Count; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000494:pharmacology; D019041:L-Selectin; D007958:Leukocyte Count; D018655:Lymphocyte Count; D016177:Macrophage-1 Antigen / Q000097:blood; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology*; D016897:Respiratory Burst; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D000199:Actins; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide