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

doi:10.1177/1753425913488012

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

Research output: Contribution to journal › Article › Academic › peer-review

6 Citations (Web of Science)

Abstract

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 language	English
Pages (from-to)	192-199
Journal	Innate Immunity
Volume	20
Issue number	2
DOIs	https://doi.org/10.1177/1753425913488012
Publication status	Published - Feb 2014

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@article{46dc49661c0d4ca4bd660f3d22c359d9,

title = "Surfactant protein A binds TGF-beta 1 with high affinity and stimulates the TGF-beta pathway",

abstract = "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.",

author = "Willems, {Coen H. M. P.} and Zimmermann, {Luc J. I.} and Nico Kloosterboer and Kramer, {Boris W.} and {van Iwaarden}, {J. Freek}",

year = "2014",

month = feb,

doi = "10.1177/1753425913488012",

language = "English",

volume = "20",

pages = "192--199",

journal = "Innate Immunity",

issn = "1753-4259",

publisher = "SAGE Publications Inc.",

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TY - JOUR

T1 - Surfactant protein A binds TGF-beta 1 with high affinity and stimulates the TGF-beta pathway

AU - Willems, Coen H. M. P.

AU - Zimmermann, Luc J. I.

AU - Kloosterboer, Nico

AU - Kramer, Boris W.

AU - van Iwaarden, J. Freek

PY - 2014/2

Y1 - 2014/2

N2 - 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.

AB - 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.

U2 - 10.1177/1753425913488012

DO - 10.1177/1753425913488012

M3 - Article

C2 - 23685990

SN - 1753-4259

VL - 20

SP - 192

EP - 199

JO - Innate Immunity

JF - Innate Immunity

IS - 2

ER -