Decreased Superoxide Anion and Hydrogen Peroxide Production by Neutrophils and Monocytes in Human Immunodeficiency Virus-Infected Children and Adults

Chen, T P; Roberts, Robert L.; Wu, Kent; Ank, Bonnie J.; Stiehm, E. Richard

doi:10.1203/00006450-199310000-00032

Cited by 39 publications

(37 citation statements)

References 23 publications

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“…Furthermore, phagocytosis and killing of Staphylococcus aureus were significantly reduced compared with controls (3). Finally, PMN superoxide activity, which is instrumental in microbicidal activity, was also shown to be depressed in PMN from HIVinfected subjects (4,5). Clinically, impaired PMN function in these patients is associated with an increased prevalence of pyogenic infections (6).…”

Section: Introductionmentioning

confidence: 92%

Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

Coffey¹,

Phare²,

George³

et al. 1998

J. Clin. Invest.

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Neutrophil (PMN) dysfunction occurs in HIV infection. Leukotrienes (LT) are mediators derived from the 5-lipoxygenase (5-LO) pathway that play a role in host defense and are synthesized by PMN. We investigated the synthesis of LT by PMN from HIV-infected subjects. There was a reduction (4.0 Ϯ 1.3% of control) in LT synthesis in PMN from HIV-infected compared with normal subjects. This was associated with reduced expression of 5-LO-activating protein (31.2 Ϯ 9.6% of normal), but not of 5-LO itself. Since HIV does not directly infect PMN, we considered that these effects were due to reduced release of cytokines, such as granulocyte colony-stimulating factor (G-CSF). We examined the effect of G-CSF treatment (300 g daily for 5 d) on eight HIV-infected subjects. PMN were studied in vitro before therapy (day 1) and on days 4 and 7. LTB 4 synthesis was increased on day 4 of G-CSF treatment, and returned toward day 1 levels on day 7. 5-LO and 5-LO-activating protein expression were increased in parallel. As a functional correlate to this increase in PMN LT synthesis by G-CSF, we examined the effects on killing of Cryptococcus neoformans . Anticryptococcal activity of PMN from HIV-infected subjects was less than that of PMN from normal subjects. G-CSF treatment improved fungistatic activity of PMN. This increase in antifungal activity was attenuated by in vitro treatment with the LT synthesis inhibitor, MK-886. In conclusion, PMN from HIV-infected subjects demonstrate reduced 5-LO metabolism and antifungal activity in vitro, which was reversed by in vivo G-CSF therapy. ( J. Clin. Invest. 1998. 102:663-670.)

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Section: Introductionmentioning

confidence: 92%

Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

Coffey¹,

Phare²,

George³

et al. 1998

J. Clin. Invest.

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“…Functional defects in neutrophils from HIV-1-infected adults have also been observed in a number of studies, and these include defects in phagocytosis (16,35), chemotaxis (6,24,40), oxidative burst (4,29,35), bacterial killing (6,26), and degranulation (23). Furthermore, dysregulation of IL-8 production (18,22,38) and the altered expression of both IL-8 receptors (24) have been reported in HIV-1-infected patients.…”

mentioning

confidence: 99%

“…When neutrophils undergo respiratory burst a series of toxic oxygen intermediates are produced, while nonoxidative mechanisms rely on the actions of potent antimicrobial polypeptides contained within cytoplasmic granules (17). A number of these responses are mediated by a variety of molecules, the most important being interleukin-8 (IL-8), leukotriene B 4 , anaphylatoxin complement 5a (C5a), N-formylmethionyl-leucyl-phenylalanine, and platelet-activating factor. IL-8, a member of the C-X-C chemokine subfamily, has a number of important biologic actions on neutrophils, including the induction of chemotaxis (19), induction of respiratory burst (41), and promotion of the release of lysosomal enzymes.…”

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confidence: 99%

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

Meddows‐Taylor

Kuhn

Meyers

et al. 2001

Clin Diagn Lab Immunol

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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.

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“…Interestingly, a nonprotective role of PMNs has also been surmised for women who received an intravaginal Candida challenge, in whom protection against infection was noninflammatory while symptomatic infection correlated with a vaginal infiltration of PMNs and a high vaginal C. albicans burden (22). In several investigations producing conflicting results, the oxidative burst of PMNs from HIV-infected patients has been found to be unchanged (49), increased (4,16,45), or decreased (11,34,37,48) compared to that of PMNs from patients uninfected with HIV. Likewise, growth inhibition of C. albicans by PMNs was found to be preserved in HIV infection (8), while phagocytosis and killing of C. albicans by PMNs were determined to be either unchanged, impaired, or increased (4,17,33,34,45,49).…”

Section: Discussionmentioning

confidence: 99%

CD8⁺T Cells but Not Polymorphonuclear Leukocytes Are Required To Limit Chronic Oral Carriage ofCandida albicansin Transgenic Mice Expressing Human Immunodeficiency Virus Type 1

Marquis¹,

Lewandowski²,

Dugas³

et al. 2006

Infect Immun

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Decreased Superoxide Anion and Hydrogen Peroxide Production by Neutrophils and Monocytes in Human Immunodeficiency Virus-Infected Children and Adults

Cited by 39 publications

References 23 publications

Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

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

CD8⁺T Cells but Not Polymorphonuclear Leukocytes Are Required To Limit Chronic Oral Carriage ofCandida albicansin Transgenic Mice Expressing Human Immunodeficiency Virus Type 1

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Decreased Superoxide Anion and Hydrogen Peroxide Production by Neutrophils and Monocytes in Human Immunodeficiency Virus-Infected Children and Adults

Cited by 39 publications

References 23 publications

Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

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

CD8+T Cells but Not Polymorphonuclear Leukocytes Are Required To Limit Chronic Oral Carriage ofCandida albicansin Transgenic Mice Expressing Human Immunodeficiency Virus Type 1

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CD8⁺T Cells but Not Polymorphonuclear Leukocytes Are Required To Limit Chronic Oral Carriage ofCandida albicansin Transgenic Mice Expressing Human Immunodeficiency Virus Type 1