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

Abstract

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.

Enhanced activation of platelets with abnormal release of RANTES in human immunodeficiency virus type 1 infection

“…However, platelet activation may also be related to other manifestations of immunological hyperactivity characteristic of HIV-1 infection. Monocytes and neutrophils, which are persistently activated during HIV-1 infection (25,40), and several inflammatory cytokines (e.g., IL-1 and TNF-a) known to be raised during HIV-1 infection (18,25) appear to promote platelet activation (5,41). Indeed, in the present study there was a significant positive correlation between plasma levels of TNF-a and both the expression of P-selectin on the platelet surface and the amount of microvesicles.…”

Mechanisms of neutrophil death in human immunodeficiency virus-infected patients: role of reactive oxygen species, caspases and map kinase pathways

“…Previous [29] and present results show that neutrophils from HIV-infected patients have increased baseline levels of superoxide production, particularly before AIDS is established. Additionally, previous reports have also shown that part of the dysfunction observed in neutrophils from HIVinfected patients is secondary to an altered ROS production [35].…”

“…As described previously, phagocytes from HIV-infected patients produce altered levels of superoxide, particularly before acquired immunodeficiency syndrome (AIDS) is established [29,30]. We observed that both freshly isolated and 6 h cultured neutrophils from HIV-infected patients produce increased levels of superoxide when compared with control individuals: 7·3 Ϯ 3·9 versus 2·9 Ϯ 0·8 and 10·1 Ϯ 1·6 versus 4·1 Ϯ 1·5, respectively ( Fig.…”

Neutrophil adhesion molecules in HIV disease

“…Three previous reports of leucocyte adhesion molecules in HIV-infected individuals have appeared [14][15][16] and only two of these studied neutrophils. In one, of 42 HIV þ subjects, there were no data concerning risk group, prescribed and unprescribed drug (opiate and NSAID) use, disease stage or presence or absence of intercurrent infections [14]. However, their finding of impaired Lselectin shedding concurs with our own.…”