title: Surfactant protein A binds TGF-β1 with high affinity and stimulates the TGF-β pathway.
abstract: We were able to demonstrate reversible, specific and high-affinity binding of radioactively-labelled TGF-β1 ((125)I-TGF-β1) to immobilized surfactant protein A (SP-A), with an apparent dissociation constant of 53 picomolar at ∼21. Addition of a 200-fold molar excess of the latency associated peptide (LAP) prevented and dissociated the binding of (125)I-TGF-β1 to SP-A, whereas latent TGF-β1 had no effect. Using a bioassay for TGF-β1 activity--a luciferase reporter assay--we were able to show that SP-A in the presence of TGF-β1 stimulated the TGF-β1 pathway, whereas SP-A alone had no effect. Studies with structural analogues of the distinct SP-A tail domain and head domain indicated that stimulatory activity of SP-A resided in the head domain. No activation of latent TGF-β1 by SP-A was observed. In addition, we observed that SP-A inhibited TGF-β1 inactivation by LAP. These results indicate that SP-A may have a regulatory role in the TGF-β1-mediated processes in the lung.
authors.affiliation: Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Coen H M P
authors.initials: CH
authors.lastname: Willems
authors.forename: Luc J I
authors.initials: LJ
authors.lastname: Zimmermann
authors.forename: Nico
authors.initials: N
authors.lastname: Kloosterboer
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: J Freek
authors.initials: JF
authors.lastname: van Iwaarden
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011498:Protein Precursors / Q000276:immunology / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D040681:Structural Homology, Protein; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D010455:Peptides; D011498:Protein Precursors; D037662:Pulmonary Surfactant-Associated Protein A; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C472416:latency-associated propeptide, TGF-beta
keywords: Collectin; fibrosis; innate immunity