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J Immunol. 2002 Jun 15;168(12):5989-92.

Cutting edge: the immunostimulatory activity of the lung surfactant protein-A involves Toll-like receptor 4.

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Unité de Défense Innée et Inflammation, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Unité 485, Paris, France.


The collectin surfactant protein-A (SP-A) is involved in the innate host defense and the regulation of inflammatory processes in the lung. In this work we investigated the molecular mechanisms related to the immunostimulatory activity of SP-A using macrophages from C3H/HeJ mice, which carry an inactivating mutation in the Toll-like receptor (TLR)4 gene, and TLR4-transfected Chinese hamster ovary cells. We demonstrate that SP-A-induced activation of the NF-kappaB signaling pathway and up-regulation of cytokine synthesis such as TNF-alpha and IL-10 are critically dependent on the TLR4 functional complex. These findings support the concept that TLR4 is a pattern recognition receptor that signals in response to both foreign pathogens and endogenous host mediators.

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