Surfactant Protein A Influences Reepithelialization in an Alveolocapillary Model System

Coen H. M. P. Willems, Luc J. I. Zimmermann, Renate M. R. Langen, Maria J. A. van den Bosch, Nico Kloosterboer, Boris W. Kramer, J. Freek van Iwaarden*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Restoring the barrier integrity of the alveolar epithelium after injury is pivotal. In the current study, we evaluated the effects of surfactant, surfactant protein A (SP-A), transforming growth factor beta (TGF-beta), and analogues of SP-A on alveolar epithelial repair. Additionally, we assessed the influence of microvascular endothelial cells on reepithelialization. Repair was studied in an in vitro model system consisting of a bilayer coculture of A549 and human pulmonary microvascular endothelial cells (HPMECs), which stably expressing fluorescent proteins. The epithelial repair was assessed in a scratch assay using vital fluorescence microscopy and compared with a monolayer of A549 cells. HMPEC cells differentially modulated the response of the A549 cells. Surfactant and SP-A augmented the reepithelialization in the presence of HPMECs, whereas in the absence of HPMECs, surfactant inhibited wound healing and SP-A failed to alter the response. Like SP-A, a structural analogue of its collagenous tail domain augmented the reepithelialization in the model system, whereas an analogue of its head domain did not alter the response. Additionally, we demonstrated that TGF-beta associated with SP-A was able to initiate the Smad-dependent TGF-beta pathway and that both TGF-beta and TGF-beta free SP-A were able to stimulate wound healing in the bilayer model. These data show that surfactant, SP-A and TGF-beta, influence epithelial repair in vitro and that the microvascular endothelial cells can modulate the response. This indicates that surfactant and SP-A could play a role in alveolar epithelial repair and that the microvascular endothelium may be involved in these processes.
Original languageEnglish
Pages (from-to)661-669
Issue number6
Publication statusPublished - Dec 2012


  • Acute lung injury
  • Acute respiratory distress syndrome
  • Pulmonary surfactant
  • Collectin
  • Wound healing

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