Surfactant protein A binds TGF-beta 1 with high affinity and stimulates the TGF-beta pathway

Coen H. M. P. Willems, Luc J. I. Zimmermann, Nico Kloosterboer, Boris W. Kramer, J. Freek van Iwaarden*

*Corresponding author for this work

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6 Citations (Web of Science)


We were able to demonstrate reversible, specific and high-affinity binding of radioactively-labelled TGF-?1 ((125)I-TGF-?1) 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-?1 to SP-A, whereas latent TGF-?1 had no effect. Using a bioassay for TGF-?1 activity--a luciferase reporter assay--we were able to show that SP-A in the presence of TGF-?1 stimulated the TGF-?1 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-?1 by SP-A was observed. In addition, we observed that SP-A inhibited TGF-?1 inactivation by LAP. These results indicate that SP-A may have a regulatory role in the TGF-?1-mediated processes in the lung.
Original languageEnglish
Pages (from-to)192-199
JournalInnate Immunity
Issue number2
Publication statusPublished - Feb 2014

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