Abstract
Pulmonary surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules. However, there is extrapulmonary existence, especially in the amniotic fluid and at the feto-maternal interface. There is sufficient evidence to suggest that SP-A and SP-D are involved in the initiation of labour. This is of great importance given that preterm birth is associated with increased mortality and morbidity. In this study, we investigated the effects of recombinant forms of SP-A and SP-D (rhSP-A and rhSP-D, the comprising of trimeric lectin domain) on contractile events in vitro, using a human myometrial cell line (ULTR) as an experimental model. Treatment with rhSP-A or rhSP-D increased the cell velocity, distance travelled and displacement by ULTR cells. rhSP-A and rhSP-D also affected the contractile response of ULTRs when grown on collagen matrices showing reduced surface area. We investigated this effect further by measuring contractility-associated protein (CAP) genes. Treatment with rhSP-A and rhSP-D induced expression of oxytocin receptor (OXTR) and connexin 43 (CX43). In addition, rhSP-A and rhSP-D were able to induce secretion of GROα and IL-8. rhSP-D also induced the expression of IL-6 and IL-6 Ra. We provide evidence that SP-A and SP-D play a key role in modulating events prior to labour by reconditioning the human myometrium and in inducing CAP genes and pro-inflammatory cytokines thus shifting the uterus from a quiescent state to a contractile one.
Highlights
Preterm labour is one of the leading causes of perinatal mortality and morbidity, and accounts for most new-born deaths as well as in children less than 5 years old [1]
It has been proposed that surfactant proteins surfactant proteins A (SP-A) and SP-D secreted into the amniotic fluid can play a key role in parturition
We elucidated the effects of SP-A and SP-D using a human myometrial cell line as an experimental model
Summary
Preterm labour is one of the leading causes of perinatal mortality and morbidity, and accounts for most new-born deaths as well as in children less than 5 years old [1]. Surfactant proteins SP-A and SP-D are collagen-containing, Ca2+-dependent C-type lectins, called collectins and are mainly produced by type II alveolar cells and non-ciliated bronchiolar epithelial cells [6] Their primary structure is characterised by an N-terminal, triple-helical collagen region and a C-terminal carbohydrate recognition domain (CRD) which is trimerised by a coiled-coil neck region between the collagen and the CRD region [7]. This family includes surfactant proteins A (SP-A) and D (SP-D) which can have a dual effect, either anti-inflammatory or pro-inflammatory, depending on their orientation and the receptors they bind to [8]
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