Surfactant protein A, an innate immune factor, is expressed in the vaginal mucosa and is present in vaginal lavage fluid

Abstract

Summary Surfactant protein A (SP‐A), first identified as a component of the lung surfactant system, is now recognized to be an important contributor to host defence mechanisms. SP‐A can facilitate phagocytosis by opsonizing bacteria, fungi and viruses, stimulate the oxidative burst by phagocytes and modulate pro‐inflammatory cytokine production by phagocytic cells. SP‐A can also provide a link between innate and adaptive immune responses by promoting differentiation and chemotaxis of dendritic cells. Because of the obvious relevance of these mechanisms to the host defence and ‘gate keeping’ functions of the lower genital tract, we examined human vaginal mucosa for SP‐A protein and transcripts and analysed vaginal lavage fluid for SP‐A. By immunocytochemistry, SP‐A was identified in two layers of the vaginal epithelium: the deep intermediate layer (the site of newly differentiated epithelial cells); and the superficial layer (comprising dead epithelial cells), where SP‐A is probably extracellular and associated with a glycocalyx. Transcripts of SP‐A were identified by Northern blot analysis in RNA isolated from vaginal wall and shown, by sequencing of reverse transcription–polymerase chain reaction products, to be derived from each of the two closely related SP‐A genes, SP‐A1 and SP‐A2. SP‐A was identified in vaginal lavage fluid by two‐dimensional gel electrophoresis, and confirmed by mass spectrometry. This study provides evidence, for the first time, that SP‐A is produced in a squamous epithelium, namely the vaginal mucosa, and has a localization that would allow it to contribute to both the innate and adaptive immune response. The findings support the hypothesis that in the vagina, as in lung, SP‐A is an essential component of the host‐defence system. A corollary hypothesis is that qualitative and quantitative alterations of normal SP‐A may play a role in the pathogenesis of lower genital tract inflammatory conditions.

Surfactant Protein A Binds to HIV and Inhibits Direct Infection of CD4+ Cells, but Enhances Dendritic Cell-Mediated Viral Transfer

“…Although SP-A has been shown to bind to a number of pathogens, its identification in biological fluids and at important sites for HIV transmission and disease progression such the lungs (10), amniotic fluid (11), and recently vaginal fluid and the female genitourinary tract (12), suggests that the collectin may potentially play an important immunological role in early phase, late-term, and perinatal transmission of HIV in vivo. In addition, the high level of glycosylation on the gp120 envelope protein of HIV known as a glycan shield, which is critical for its proper folding and evasion from the host immune response, would make it a prime target for the SP-A CRDs (13).…”

Humanized SFTPA1 and SFTPA2 Transgenic Mice Reveal Functional Divergence of SP-A1 and SP-A2

“…SP-A1 (6A, 6A 2 , 6A 3 , and 6A 4 ) and SP-A2 (1A, 1A 0 , 1A 1 , 1A 2 , 1A 3 , and 1A 5 )); these are observed at greater than 1% frequency in the population (13). Human SP-A is expressed in alveolar epithelial type II cells (14) and in tracheal and bronchial submucosal gland cells in lung as well as in other tissues (15)(16)(17)(18). SP-A1 and SP-A2 are expressed in the type II cells; SP-A2 is expressed in human tracheal and bronchial submucosal gland cells (15,18).…”

Pulmonary Surfactant Protein A Is Expressed in Mouse Retina by Muller Cells and Impacts Neovascularization in Oxygen-Induced Retinopathy

“…[7][8][9] Interestingly, these molecules have been found in organs other than those in the pulmonary system. [10][11][12] SP-A has been identified in vaginal and amniotic fluid, synovial fluid, the gastrointestinal tract, and the ocular surface, 13 thus broadening the possible function of these immunity-regulating proteins. SP-A on the corneal surface has been found to be an important mediator of bacterial clearance in the lacrimal/ocular system.…”