Effects of candidate vaginally-applied microbicide compounds on innate immune cells

Milligan, Gregg N.; Young, Christal G.; Meador, Michael G.; Chu, Chin Fun; Stanberry, Lawrence R.

doi:10.1016/j.jri.2005.04.003

Cited by 6 publications

(2 citation statements)

References 28 publications

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“…An increase in CD11b + /CD14 + macrophages/monocytes was also detectable in vaginal surface cytobrush samples. The increase in CD11b + /CD14 + macrophages/monocytes is in agreement with a finding by Milligan and co-workers, who observed larger numbers of F4/80 + macrophages in a mouse model of vaginal irritation after treatment with cholic acid [40, 41]. The histopathological score of the vaginal tissue after N-9 treatment increased insignificantly, although the number of CD11b + macrophages was significantly increased.…”

Section: Discussionsupporting

confidence: 91%

Increased CCL2 Expression and Macrophage/Monocyte Migration During Microbicide-Induced Vaginal Irritation

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Harrison

Dousman

et al. 2009

CHR

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Despite availability of successful prevention strategies, HIV continues to spread at alarming rates, especially among women in developing countries. Vaginal microbicides offer a promising approach for blocking transmission of HIV when condom use cannot be negotiated with male partners. A major problem in the development of vaginal microbicides is chemically induced vaginal irritation, which can enhance the risk of HIV transmission. Evaluation of vaginal irritation prior to clinical trials typically uses an expensive and animal-intensive rabbit vaginal irritation model, which could be supplemented by measuring additional inflammatory biomarkers. We studied several immunological parameters as potential biomarkers of vaginal irritation, using the spermicides nonoxynol-9 and benzalkonium chloride as test microbicides. We measured amounts of cytokines, as well as inflammatory cells, in vaginal tissue lysates and on the vaginal surface. We observed that treatment with the selected microbicides increases quantities of the inflammatory cytokines interleukin-1β, CXCL8, and CCL2 in the vaginal tissue parenchyma, and of CCL2 on the vaginal surface. This observation was correlated with increases in macrophages in the vaginal parenchyma. We suggest that measurements of CCL2 and macrophages can serve as new inflammatory biomarkers to evaluate the safety of promising novel microbicides for prevention of HIV.

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Section: Discussionsupporting

confidence: 91%

Increased CCL2 Expression and Macrophage/Monocyte Migration During Microbicide-Induced Vaginal Irritation

Alt

Harrison

Dousman

et al. 2009

CHR

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“…33 The mechanism of carrageenans differs from that of LPS, which was exemplified by Nacife and coauthors 6 showing the morphological characteristics of activated monocytes and macrophages depended on the nature of these triggering stimuli. Milligan et al 34 in turn reported that pretreatment of innate immune cells normally found in the vaginal mucosa with carrageenans did not alter their composition or phagocytosis function against fluorochromelabeled bacteria. These results correlated with the findings of Sugita-Konishi and coauthors 35 in which the ability of macrophage-like cell lines to phagocytize bacteria was not inhibited by lambda or kappa carrageenan.…”

Section: Discussionmentioning

confidence: 99%

Carrageenans effect on neutrophils alone and in combination with LPS in vitro

Sokolova

Karetin

Давыдова

et al. 2016

J Biomedical Materials Res

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Influence of sulfated red algal polysaccharides (κ-, λ-, and κ/β-carrageenans) and degraded derivative of κ/β-carrageenan on neutrophils/monocytes activation alone and in combination with lipopolysaccharide was investigated by means of determination of reactive oxygen species production, latex microparticles engulfment, total and extracellular myeloperoxidase induction and the analysis of silhouette and contour two-dimensional images of flattened cells. Carrageenans alone can activate neutrophils with much less potency than lipopolysaccharide (LPS) and the sulfation degree of carrageenans stipulates high activity in this role. On the other hand, carrageenans especially with low contents of sulfate groups are able to interfere with LPS in vitro resulting in reducing inter- and intracellular activation of neutrophils killing mechanisms. Further research is necessary to relate these findings to actions on the whole animal or human in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1603-1609, 2016.

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Preclinical evaluation of anti-HIV microbicide products: New models and biomarkers

Doncel

Clark

2010

Antiviral Research

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Effects of candidate vaginally-applied microbicide compounds on innate immune cells

Cited by 6 publications

References 28 publications

Increased CCL2 Expression and Macrophage/Monocyte Migration During Microbicide-Induced Vaginal Irritation

Increased CCL2 Expression and Macrophage/Monocyte Migration During Microbicide-Induced Vaginal Irritation

Carrageenans effect on neutrophils alone and in combination with LPS in vitro

Preclinical evaluation of anti-HIV microbicide products: New models and biomarkers

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