Am. J. Respir. Cell Mol. Biol., Vol 12, No. 4, Apr 1995, 449-454.
Induction of lipopolysaccharide-binding protein gene expression in cultured rat pulmonary artery smooth muscle cells by interleukin 1 beta
HR Wong, BR Pitt, GL Su, DP Rossignol, AR Steve, TR Billiar and SC Wang
Department of Anesthesiology, University of Pittsburgh School of Medicine, USA.
Lipopolysaccharide (LPS)-binding protein (LBP) binds with high affinity to
LPS, and the LBP-LPS complex enhances cellular inflammatory responses to
LPS. Although it is present in normal serum, LBP is also induced as part of
the acute phase response. Synthesis of LBP is though to be limited to the
liver, but we have recently reported significant extrahepatic (including
pulmonary) LBP mRNA expression in in vivo rat models of sepsis and
inflammation. In the present study, we tested the hypothesis that a
cellular source of pulmonary LBP in the rat may be vascular smooth muscle,
by exposing cultured rat pulmonary artery smooth muscle cells (RPASMC) to
cytokines and LPS. Treatment of RPASMC for 4 and 24 h with a combination of
tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), interferon
gamma, and LPS resulted in significant LBP mRNA expression. Of this
mixture, IL-1 beta alone was sufficient to induce LBP mRNA expression in
both a time- and dose- dependent manner. The effects of IL-beta on LBP mRNA
expression were significantly antagonized by IL-1 receptor antagonist
protein. Furthermore, supernatants from RPASMC treated with IL-1 beta
enhanced the binding of [125I]ASD-LPS by the macrophage cell line RAW
264.7, indicative of LBP bioactivity. We conclude that pulmonary artery
smooth muscle cells stimulated with IL-1 beta produce a transcript for LBP
or a homologous product in vitro. Local production of LBP could play an
important role in the pulmonary response to inflammation and sepsis.
