Defective neutrophil degranulation induced by interleukin-8 and complement5a and down-regulation of associated receptors in children vertically infected with human immunodeficiency virus type 1

The polymorphonuclear neutrophils (PMNs) of patients infected with human im munodeficiency virus type 1 (HIV-1) show impaired microbicidal responses. T he present study assessed the functional integrity of PMN degranulation res ponses and the expression of specific receptors that mediate these response s in a group of children vertically infected with HIV-1, PMN degranulation in response to interleukin-8 (IL-8) and complement 5a (C5a) was measured in a group of HIV-1-infected children with mild and severe clinical disease a nd in an uninfected control group. In addition, the expression of CXCR1, CX CR2, and CD88 on whole-blood PMNs was quantified by flow cytometry, Althoug h CXCR1 expression was found to be largely unaltered in the HIV-1-infected children relative to that in the control children, the intensity of CXCR2 e xpression was significantly reduced in those with severe disease. Furthermo re, there was a significant reduction in the percentage of cells expressing CD88 and in the intensity of CD88 fluorescence in the HIV-1-infected child ren compared to that in control children, with CD88 fluorescence intensity more significantly reduced in the presence of severe disease. PMNs from a l arge proportion of the HIV-1-infected children either showed reciprocal deg ranulation responses or were unresponsive to IL-8 and C5a, whereas the PMNs from the uninfected children showed positive responses. Inefficient agonis t-induced degranulation may contribute to the increased susceptibility of H IV-1-infected children to secondary microbial infections. Furthermore, redu ced expression of CXCR2 and CD88 may be suggestive of defects in other func tions of PMNs from HTV-1-infected children.