Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle

Moriyama, Akihiro; Shimoya, Koichiro; Ogata, Isao; Kimura, Tadashi; Nakamura, Takafumi; Wada, Hiroyoshi; Ohashi, Kazutomo; Azuma, Chihiro; Saji, Fumitaka; Murata, Yuji

doi:10.1093/molehr/5.7.656

Cited by 89 publications

(65 citation statements)

References 17 publications

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“…The cervical tube full of mucus migrating outwards over time makes for a formidable barrier for the virus. Furthermore, mucus contains antiviral proteins that may play an inhibitory role in HIV-1 transmission, as endocervical tissue can produce peptide defensins and secretory leukocyte protease inhibitors that inhibit HIV-1 infection (39). Overall, these inefficient interactions of virus to overcome both intact mucosal barriers are in agreement with known characteristics of transmission: the ability of a small number of virions to initiate transmission is consistent with low per coital transmission rates, especially under conditions of chronic infection in discordant, heterosexual couples (30,40).…”

Section: Discussionmentioning

confidence: 99%

Defining the Interaction of HIV-1 with the Mucosal Barriers of the Female Reproductive Tract

Carias

McCoombe

McRaven

et al. 2013

J Virol

141

170

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e Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4؉ target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.

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Section: Discussionmentioning

confidence: 99%

Defining the Interaction of HIV-1 with the Mucosal Barriers of the Female Reproductive Tract

Carias

McCoombe

McRaven

et al. 2013

J Virol

141

170

View full text Add to dashboard Cite

show abstract

“…For example, the concentration of HD-5 produced by endometrial epithelial cells is highest during the secretory and post-ovulatory stage of the menstrual cycle. 52 SLPI levels also vary throughout the menstrual cycle in the cervical mucus but not in serum, 53 and the concentrations of a-defensins and b-defensins in cervicovaginal lavage (CVL) from normal patients can vary by up to 50-fold, suggesting hormonal regulation of antimicrobial peptides. 8 In the endometrium, levels of HBDs and SLPI are under cycle control, and levels of SLPI are highest during the secretory phase.…”

Section: Antimicrobial Peptides and Proteins Are Principal Effector Mmentioning

confidence: 99%

REVIEW ARTICLE: Antimicrobial Polypeptides are Key Anti‐HIV‐1 Effector Molecules of Cervicovaginal Host Defense

Cole

2007

American J Rep Immunol

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Mucosal surfaces of the cervix and vagina are portals for heterosexual transmission of human immunodeficiency virus type 1 (HIV‐1) and, therefore, play a fundamental role in the pathogenesis of primary infection. Cationic antimicrobial polypeptides including defensins are the principal effector molecules of mucosal innate immunity against microbes and viruses such as HIV. In cervicovaginal secretions, antimicrobial polypeptides constitute the majority of the intrinsic anti‐HIV‐1 activity, synergism between cationic polypeptides is complex, and full anti‐HIV‐1 activity involves the complete complement of cationic polypeptides. Periods in which cationic antimicrobial polypeptide expression is reduced are likely associated with increased susceptibility to HIV‐1 infection. This review provides an overview of the role of cationic antimicrobial polypeptides in innate cervicovaginal anti‐HIV‐1 host defense, and discusses how hormones and bacterial infections can regulate their expression. Emphasis is placed on the θ‐defensin (retrocyclin) class of anti‐HIV‐1 peptides and their potential for development as topical microbicides to prevent HIV‐1 transmission.

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“…In fact, altered mucus properties have been shown to be a very good predictor of the fertile window (1). The importance of the cervical mucus is also illustrated by the observation that abnormalities of the cervical secretions are responsible for infertility in about 5-10% of infertile women (2).…”

mentioning

confidence: 99%

Large Scale Identification of Proteins, Mucins, and Their O-Glycosylation in the Endocervical Mucus during the Menstrual Cycle

Andersch-Björkman

Thomsson

Larsson

et al. 2007

Molecular & Cellular Proteomics

165

156

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The mucus filling the human cervical opening blocks the entry to the uterus, but this has to be relative and allow for the sperm to penetrate at ovulation. We studied this mucus, its content of proteins and mucins, and the mucin O-glycosylation in cervical secretions before, during, and after ovulation. Cervical mucosal secretions from 12 subjects were collected, reduced-alkylated, separated with polyacrylamide or agarose/polyacrylamide gel electrophoresis, and stained with silver, Alcian blue, or Coomassie Blue stain. Protein and mucin bands from before and during ovulation were digested and subsequently analyzed by nano-LC-FT-ICR MS and MS/MS. We identified 194 proteins after searches against the NCBI non-redundant protein database and an in-house mucin database. Three gel-forming (MUC5B, MUC5AC, and MUC6) and two transmembrane mucins (MUC16 and MUC1) were identified. For the analysis of mucin O-glycosylation, separated mucins from six individuals were blotted to PVDF membranes, and the O-glycans were released by reductive ␤-elimination and analyzed with capillary HPLC-MS and -MS/MS. At least 50 neutral, sialic acid-, and sulfate-containing oligosaccharides were found. An increase of GlcNAc-6GalNAcol Core 2 structures and a relative decrease of NeuAc residues are typical for ovulation, and NeuAc6GalNAcol and NeuAc-3Gal-epitopes are typical for the non-ovulatory phases. The cervical mucus at ovulation is thus characterized by a relative increase in neutral fucosylated oligosaccharides. This comprehensive characterization of the mucus during the menstrual cycle suggests mucin glycosylation as the major alteration at ovulation, but the relation to the altered physicochemical properties and sperm penetrability is still not understood.

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Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle

Cited by 89 publications

References 17 publications

Defining the Interaction of HIV-1 with the Mucosal Barriers of the Female Reproductive Tract

Defining the Interaction of HIV-1 with the Mucosal Barriers of the Female Reproductive Tract

REVIEW ARTICLE: Antimicrobial Polypeptides are Key Anti‐HIV‐1 Effector Molecules of Cervicovaginal Host Defense

Large Scale Identification of Proteins, Mucins, and Their O-Glycosylation in the Endocervical Mucus during the Menstrual Cycle

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