title: Defective neutrophil degranulation induced by interleukin-8 and complement 5a and down-regulation of associated receptors in children vertically infected with human immunodeficiency virus type 1.
abstract: The polymorphonuclear neutrophils (PMNs) of patients infected with human immunodeficiency virus type 1 (HIV-1) show impaired microbicidal responses. The present study assessed the functional integrity of PMN degranulation responses and the expression of specific receptors that mediate these responses 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 and in an uninfected control group. In addition, the expression of CXCR1, CXCR2, and CD88 on whole-blood PMNs was quantified by flow cytometry. Although 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 expression was significantly reduced in those with severe disease. Furthermore, there was a significant reduction in the percentage of cells expressing CD88 and in the intensity of CD88 fluorescence in the HIV-1-infected children compared to that in control children, with CD88 fluorescence intensity more significantly reduced in the presence of severe disease. PMNs from a large proportion of the HIV-1-infected children either showed reciprocal degranulation responses or were unresponsive to IL-8 and C5a, whereas the PMNs from the uninfected children showed positive responses. Inefficient agonist-induced degranulation may contribute to the increased susceptibility of HIV-1-infected children to secondary microbial infections. Furthermore, reduced expression of CXCR2 and CD88 may be suggestive of defects in other functions of PMNs from HIV-1-infected children.
authors.affiliation: AIDS Virus Research Unit, National Institute for Virology, Johannesburg, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Meddows-Taylor
authors.forename: L
authors.initials: L
authors.lastname: Kuhn
authors.forename: T M
authors.initials: TM
authors.lastname: Meyers
authors.forename: G
authors.initials: G
authors.lastname: Sherman
authors.forename: C T
authors.initials: CT
authors.lastname: Tiemessen
mesh_terms: D000367:Age Factors; D015703:Antigens, CD / Q000096:biosynthesis*; D018791:CD4 Lymphocyte Count; D015550:Cell Degranulation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015936:Complement C5a / Q000276:immunology* / Q000494:pharmacology; D015536:Down-Regulation / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D016209:Interleukin-8 / Q000276:immunology* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis*; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis*; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D016209:Interleukin-8; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D015936:Complement C5a