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Direct Interaction of Surfactant Protein A with Myometrial Binding Sites: Signaling and Modulation by Bacterial Lipopolysaccharide¹

Equipe Endotoxines³ and Equipe Signalisation et Régulations Cellulaires,⁴ Institut de Biochimie et Biophysique Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, UMR-8619, Université Paris-Sud, 91400 Orsay, France

ABSTRACT

Surfactant protein A (SFTPA1), a member of the collagenous lectin (collectin) family, was first described as a major constituent of lung surfactant, but has recently also been found in the female genital tract. Various microorganisms colonize this area and may cause intrauterine infection or trigger preterm labor. We found that SFTPA1 was not produced in the uterus. Instead, it was immunodetected transiently in rat myometrium at the end (Days 19 and 21) of gestation, but not postpartum, and in cultured myometrial cells. Fluorescence microscopy showed that Texas Red-labeled SFTPA1 bound to myometrial cells. This result was confirmed by biochemical approaches. [¹²⁵I]-SFTPA1 bound to two myometrial cell proteins (55 and 210 kDa). This interaction was dependent on the integrity of the collagenlike domain of SFTPA1. SFTPA1 rapidly activated mitogen-activated protein kinase 1/3 (MAPK1/3) in myometrial cells. Bacterial lipopolysaccharide (LPS), an agent known to trigger uterine contractions and preterm birth, also activated MAPK1/3. The prolonged treatment of myometrial cells with LPS or SFTPA1 upregulated PTGS2 (COX2) protein levels. The addition of rough-type LPS to SFTPA1 blocked the interaction of SFTPA1 with its binding sites and the activation of MAPK1/3 and PTGS2 by SFTPA1. Our data provide the first demonstration of a direct effect of SFTPA1 on rat myometrial cells and inhibitory cross talk between SFTPA1 and LPS signals, providing new insight into the mechanisms of normal and preterm parturition.

female reproductive tract, immunology, parturition, signal transduction, uterus

¹Supported by the Fondation pour la Recherche Médicale (contract grant number ACE20040901625), the Centre National de la Recherche Scientifique, and Université Paris-Sud.

Correspondence: ²Zahra Tanfin, UMR 8619, CNRS, Batiment 430, Universite Paris Sud, 91400 Orsay, France. FAX: 33 169 853 715; e-mail: zahra.tanfin{at}ibbmc.u-psud.fr

This article has been cited by other articles:

				I. Garcia-Verdugo, Z. Tanfin, E. Dallot, M.-J. Leroy, and M. Breuiller-Fouche Surfactant Protein A Signaling Pathways in Human Uterine Smooth Muscle Cells Biol Reprod, August 1, 2008; 79(2): 348 - 355. [Abstract] [Full Text] [PDF]