Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract

• Published in: The American journal of pathology Vol. 152; no. 5; pp. 1247 - 1258
• Main Authors: Quayle, AJ, Porter, EM, Nussbaum, AA, Wang, YM, Brabec, C, Yip, KP, Mok, SC
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.05.1998; American Society for Investigative Pathology
• Subjects: Adult; Anti-Infective Agents - metabolism; Biological and medical sciences; Blood Proteins - genetics; Blood Proteins - metabolism; Blotting, Western; Cervix Uteri - secretion; Defensins; DNA Primers - chemistry; Endometrium - secretion; Epithelium - secretion; Fallopian Tubes - secretion; Female; Female genital diseases; Gene Expression; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Medical sciences; Menstrual Cycle - physiology; Microscopy, Confocal; Middle Aged; Non tumoral diseases; Polymerase Chain Reaction; RNA, Messenger - metabolism; Human; Immunohistochemistry; Menstrual cycle; Peptides; Vagina; Vaginal diseases; Inflammation; Uterine cervix; Fallopian tube; Antimicrobial agent; Female genital diseases; Polymerase chain reaction; Pathology; Uterine diseases; Immunoblotting assay; Female; Molecular biology; Defensin; Immunofluorescence; Sequencing; Endometrium; Comparative study; Fallopian tube pathology; Quantitative analysis
• ISSN: 0002-9440; 1525-2191

This study describes the novel localization of the antimicrobial peptide human intestinal defensin-5 (HD-5) in female genital tract epithelia. Using a 3' rapid amplification of cDNA ends (RACE) protocol, HD-5 was cloned from a vaginal epithelial cell RNA preparation, and its identity was confirmed by sequencing. Tissue samples from multiple donors were subsequently screened for HD-5 expression by reverse transcription polymerase chain reaction. HD-5 message was invariantly expressed by normal vagina and ectocervix and inflamed fallopian tube, but variably expressed by normal endocervix, endometrium, and fallopian tube (60, 64, and 29% of specimens, respectively). Expression in endometrium was the highest during the early secretory phase of the menstrual cycle. Using immunohistochemistry and confocal microscopy, HD-5 peptide was localized in the upper half of the stratified squamous epithelium of the vagina and ectocervix, with the intensity of cellular staining increasing toward the lumen. In positive endocervix, endometrium, and fallopian tube specimens, HD-5 was located in apically oriented granules and on the apical surface of a proportion of columnar epithelial cells. Using Western blot analysis, secreted HD-5 was detected in cervicovaginal lavages, with the highest concentrations found during the secretory phase of the menstrual cycle. We hypothesize that HD-5 is an intrinsic component of the female urogenital innate immune defense system and that its expression may be modulated by hormonal and proinflammatory factors.