Pulmonary surfactant protein a modulates the cellular response to smooth and rough lipopolysaccharides by interaction with CD14

Hitomi Sano, Hitoshi Sohma, Tatsushi Muta, Shin Ichi Nomura, Dennis R. Voelker, Yoshio Kuroki

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159 Citations (Scopus)

Abstract

Pulmonary surfactant protein A (SP-A) plays an important part in Ab- independent host defense mechanisms of the lung. In this study we investigated how SP-A interacts with distinct serotypes of bacterial LPS and modulates LPS-elicited cellular responses. SP-A bound to rough forms but not to smooth forms of LPS. In the macrophage-like cell line U937, SP-A inhibited mRNA expression and secretion of TNF-α induced by smooth LPS, but rough LPS- induced TNF-α expression was unaffected by SP-A. When U937 cells and rat alveolar macrophages were preincubated with SP-A, smooth LPS failed to induce TNF-α secretion, whereas rough LPS-induced TNF-α secretion was modestly increased. To clarify the mechanism by which SP-A modulates LPS-elicited cellular responses, we further examined the interaction of SP-A with CD14, which is known as a major LPS receptor. Western blot analysis revealed that CD14 was one of the SP-A binding proteins isolated from solubilized U937 cells. In addition, SP-A directly bound to recombinant soluble CD14 (rsCD14). When rsCD14 was preincubated with SP-A, the binding of rsCD14 to smooth LPS was significantly reduced but the association of rsCD14 with rough LPS was augmented. These results demonstrate the different actions of SP-A upon distinct serotypes of LPS and indicate that the direct interaction of SP-A with CD14 constitutes a likely mechanism by which SP-A modulates LPS-elicited cellular responses.

Original languageEnglish
Pages (from-to)387-395
Number of pages9
JournalJournal of Immunology
Volume163
Issue number1
Publication statusPublished - 1999 Jul 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sano, H., Sohma, H., Muta, T., Nomura, S. I., Voelker, D. R., & Kuroki, Y. (1999). Pulmonary surfactant protein a modulates the cellular response to smooth and rough lipopolysaccharides by interaction with CD14. Journal of Immunology, 163(1), 387-395.