title: Soluble leukocyte-Associated Ig-like Receptor-1 in amniotic fluid is of fetal origin and positively associates with lung compliance.
abstract: The soluble form of the inhibitory immune receptor leukocyte-Associated Ig-like Receptor-1 (sLAIR-1) is present in plasma, urine and synovial fluid and correlates to inflammation. We and others previously showed inflammatory protein expression in normal amniotic fluid at term. We hypothesized that sLAIR-1 is present in amniotic fluid during term parturition and is related to fetal lung function development. sLAIR-1 was detectable in all amniotic fluid samples (n=355) collected during term spontaneous deliveries. First, potential intra-uterine origins of amniotic fluid sLAIR-1 were explored. Although LAIR-1 was expressed on the surface of amniotic fluid neutrophils, LAIR-1 was not secreted upon ex vivo neutrophil stimulation with LPS, or PMA/ionomycin. Cord blood concentrations of sLAIR-1 were fourfold lower than and not related to amniotic fluid concentrations and placentas showed no or only sporadic LAIR-1 positive cells. Similarly, in post-mortem lung tissue of term neonates that died of non-pulmonary disorders LAIR-1 positive cells were absent or only sporadically present. In fetal urine samples, however, sLAIR-1 levels were even higher than in amniotic fluid and correlated with amniotic fluid sLAIR-1 concentrations. Second, the potential relevance of amniotic fluid sLAIR-1 was studied. sLAIR-1 concentrations had low correlation to amniotic fluid cytokines. We measured neonatal lung function in a convenient subset of 152 infants, using the single occlusion technique, at a median age of 34 days (IQR 30-39). The amniotic fluid concentration of sLAIR-1 was independently correlated to airway compliance (ρ=0.29, P=.001). Taken together, we show the consistent presence of sLAIR-1 in amniotic fluid, which originates from fetal urine. Concentrations of sLAIR-1 in amniotic fluid during term deliveries are independent from levels of other soluble immune mediators. The positive association between concentrations of amniotic fluid sLAIR-1 and neonatal lung compliance suggests that amniotic fluid sLAIR-1 may be useful as a novel independent marker of neonatal lung maturation.
authors.affiliation: Department of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Houben
authors.affiliation: Department of Immunology, Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marloes J M
authors.initials: MJ
authors.lastname: Olde Nordkamp
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Peter G J
authors.initials: PG
authors.lastname: Nikkels
authors.affiliation: Department of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Cornelis K
authors.initials: CK
authors.lastname: van der Ent
authors.affiliation: Department of Immunology, Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Linde
authors.initials: L
authors.lastname: Meyaard
authors.affiliation: Department of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands ; Department of Immunology, Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Bont
mesh_terms: D000653:Amniotic Fluid / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology; D008170:Lung Compliance; D009504:Neutrophils / Q000378:metabolism; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D047929:Term Birth
chemical_list: D015415:Biomarkers; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1