title: Impaired interleukin-8-induced degranulation of polymorphonuclear neutrophils from human immunodeficiency virus type 1-infected individuals.
abstract: Degranulation of peripheral blood polymorphonuclear leukocytes (PMNLs) was monitored in human immunodeficiency virus (HIV) type 1 (HIV-1)-infected individuals with or without pulmonary tuberculosis (HIV/TB and HIV groups, respectively) by measuring the release of beta-glucuronidase induced by interleukin-8 (IL-8). This was increased in a dose-dependent manner in the control groups consisting of healthy blood donors and patients with pulmonary tuberculosis. In contrast, PMNLs from the HIV and HIV/TB groups responded reciprocally in the same assay; that is, higher IL-8 input concentrations resulted in the release of less enzyme than lower IL-8 input concentrations. The degranulation response of PMNLs from HIV-1-infected individuals was similarly altered for another agonist, N-formyl-methionyl-leucyl-phenylalanine, suggesting that impairment of the nonoxidative armature of PMNL was a more generalized phenomenon. However, impaired IL-8-induced degranulation was found to be associated with the reduced expression of both IL-8 receptors, A and B, on whole-blood PMNLs from HIV-1-infected patients compared with that on whole-blood PMNLs from healthy persons. The density of IL-8RA, in particular, was most reduced on the surfaces of PMNLs from those patients with the poorest degranulation in response to IL-8. Inefficient agonist-induced degranulation may contribute to the increased susceptibility of HIV-1-infected persons to secondary microbial infections, this being further exacerbated in HIV/TB patients who, in addition, display defects in phagocytosis and oxidative burst.
authors.affiliation: MRC AIDS Virus Research Unit, National Institute for Virology, and Department of Virology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Meddows-Taylor
authors.forename: D J
authors.initials: DJ
authors.lastname: Martin
authors.forename: C T
authors.initials: CT
authors.lastname: Tiemessen
mesh_terms: D000328:Adult; D001782:Blood Donors; D015550:Cell Degranulation / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005434:Flow Cytometry; D005966:Glucuronidase / Q000378:metabolism; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology
chemical_list: D016209:Interleukin-8; D005966:Glucuronidase