title: Biomarkers of leukocyte traffic and activation in the vaginal mucosa.
abstract: Development of novel vaginal spermicides and anti-human immunodeficiency virus (HIV) microbicides requires careful assessment of their potential to recruit and activate CD4+ HIV-1 host cells in the female genital tract mucosa, two events that facilitate HIV-1 infection. Leukocyte traffic and activation are mediated by proinflammatory cytokines and chemokines, e.g. interleukin (IL)-1, IL-6 and IL-8, which have been detected in vaginal secretions in association with epithelial damage and infections. These proinflammatory mediators, however, have bidirectional, destructive as well as beneficial, effects on the mucosal barrier, and may be counterbalanced by endogenous inhibitors. Here we propose additional biomarkers for the evaluation of compound-induced cervicovaginal mucosal inflammation. Displaying different temporal patterns of detection, the levels of soluble E-selectin, vascular adhesion molecule-1, CD14 and myeloperoxidase in vaginal secretions reflected the mucosal leukocyte reaction to proinflammatory compounds being evaluated for safety in an improved rabbit vaginal irritation model. These biomarkers, which were also detected in human vaginal secretions, may be used to enhance the characterization of mucosal safety of vaginally applied compounds, both in animal as well as clinical studies.
authors.affiliation: Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Radiana T
authors.initials: RT
authors.lastname: Trifonova
authors.forename: Malini
authors.initials: M
authors.lastname: Bajpai
authors.forename: Jenna-Malia
authors.initials: JM
authors.lastname: Pasicznyk
authors.forename: Neelima
authors.initials: N
authors.lastname: Chandra
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Doncel
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D001548:Benzalkonium Compounds / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D017137:Nonoxynol / Q000633:toxicity; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D015203:Reproducibility of Results; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D013089:Spermatocidal Agents / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014627:Vaginitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000891:Anti-Infective Agents, Local; D001548:Benzalkonium Compounds; D015415:Biomarkers; D019040:E-Selectin; D018950:Lipopolysaccharide Receptors; D013089:Spermatocidal Agents; D019010:Vascular Cell Adhesion Molecule-1; D017137:Nonoxynol; D012967:Sodium Dodecyl Sulfate; D009195:Peroxidase