Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages

Shin Ichi Suga, Hiroshi Itoh, Yasato Komatsu, Hiroshi Ishida, Toshio Igaki, Jun Yamashita, Kentaro Doi, Tae Hwa Chun, Takaaki Yoshimasa, Issei Tanaka, Kazuwa Nakao

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Abstract

We demonstrated endothelial production of C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and its regulation by cytokines, including tumor necrosis factor-α (TNFα). We thus proposed that CNP can control vascular tone and growth as an endothelium-derived relaxing peptide. We also revealed the marked elevation of plasma CNP concentration in patients with septic shock, in which TNFα, plays a significant part. As the interaction between endothelial cells (EC) and monocytes-macrophages plays a pivotal role in the pathogenesis of atherosclerosis, we investigated the effect of coculture of EC and macrophages on endothelial production of CNP. We used a human monocytic leukemia cell line, THP-1, which differentiates into macrophages when treated with phorbol 12-myristate 13-acetate. The coculture of EC and THP-1-derived macrophages enhanced CNP secretion by more than 10-fold compared with the single culture of EC or the coculture of EC and THP-1 without phorbol 12- myristate 13-acetate treatment. Prevention of direct contact between EC and THP-1-derived macrophages did not attenuate the increase in CNP secretion. Northern blotting revealed the augmentation of CNP messenger RNA expression in EC in the coculture. We detected TNFα in the conditioned medium from the coculture of EC and THP-1-derived macrophages. Furthermore, anti-TNFα antibody inhibited the stimulation of CNP secretion in the coculture. CNF at a concentration of 1 nM did not stimulate cGMP production in EC or THP-1- derived macrophages, but it elevated cGMP production significantly in vascular smooth muscle cells. These results indicate that endothelial production of CNP is stimulated mainly by TNFα released from THP-1-derived macrophages in the coculture. Endothelial CNP at the enhanced level may be one of the vascular mediators to regulate local vascular tone and growth through cGMP production by vascular smooth muscle cells, suggesting the potential significance of endothelial CNP in atherosclerosis.

Original languageEnglish
Pages (from-to)1920-1926
Number of pages7
JournalEndocrinology
Volume139
Issue number4
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

C-Type Natriuretic Peptide
Endothelial Cells
Macrophages
Coculture Techniques
Tumor Necrosis Factor-alpha
Blood Vessels
Vascular Smooth Muscle
Smooth Muscle Myocytes
Atherosclerosis
Acetates
Natriuretic Peptides
Conditioned Culture Medium
Septic Shock
Growth
Northern Blotting
Endothelium
Monocytes
Leukemia

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Suga, S. I., Itoh, H., Komatsu, Y., Ishida, H., Igaki, T., Yamashita, J., ... Nakao, K. (1998). Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages. Endocrinology, 139(4), 1920-1926.

Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages. / Suga, Shin Ichi; Itoh, Hiroshi; Komatsu, Yasato; Ishida, Hiroshi; Igaki, Toshio; Yamashita, Jun; Doi, Kentaro; Chun, Tae Hwa; Yoshimasa, Takaaki; Tanaka, Issei; Nakao, Kazuwa.

In: Endocrinology, Vol. 139, No. 4, 1998, p. 1920-1926.

Research output: Contribution to journalArticle

Suga, SI, Itoh, H, Komatsu, Y, Ishida, H, Igaki, T, Yamashita, J, Doi, K, Chun, TH, Yoshimasa, T, Tanaka, I & Nakao, K 1998, 'Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages', Endocrinology, vol. 139, no. 4, pp. 1920-1926.
Suga, Shin Ichi ; Itoh, Hiroshi ; Komatsu, Yasato ; Ishida, Hiroshi ; Igaki, Toshio ; Yamashita, Jun ; Doi, Kentaro ; Chun, Tae Hwa ; Yoshimasa, Takaaki ; Tanaka, Issei ; Nakao, Kazuwa. / Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages. In: Endocrinology. 1998 ; Vol. 139, No. 4. pp. 1920-1926.
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abstract = "We demonstrated endothelial production of C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and its regulation by cytokines, including tumor necrosis factor-α (TNFα). We thus proposed that CNP can control vascular tone and growth as an endothelium-derived relaxing peptide. We also revealed the marked elevation of plasma CNP concentration in patients with septic shock, in which TNFα, plays a significant part. As the interaction between endothelial cells (EC) and monocytes-macrophages plays a pivotal role in the pathogenesis of atherosclerosis, we investigated the effect of coculture of EC and macrophages on endothelial production of CNP. We used a human monocytic leukemia cell line, THP-1, which differentiates into macrophages when treated with phorbol 12-myristate 13-acetate. The coculture of EC and THP-1-derived macrophages enhanced CNP secretion by more than 10-fold compared with the single culture of EC or the coculture of EC and THP-1 without phorbol 12- myristate 13-acetate treatment. Prevention of direct contact between EC and THP-1-derived macrophages did not attenuate the increase in CNP secretion. Northern blotting revealed the augmentation of CNP messenger RNA expression in EC in the coculture. We detected TNFα in the conditioned medium from the coculture of EC and THP-1-derived macrophages. Furthermore, anti-TNFα antibody inhibited the stimulation of CNP secretion in the coculture. CNF at a concentration of 1 nM did not stimulate cGMP production in EC or THP-1- derived macrophages, but it elevated cGMP production significantly in vascular smooth muscle cells. These results indicate that endothelial production of CNP is stimulated mainly by TNFα released from THP-1-derived macrophages in the coculture. Endothelial CNP at the enhanced level may be one of the vascular mediators to regulate local vascular tone and growth through cGMP production by vascular smooth muscle cells, suggesting the potential significance of endothelial CNP in atherosclerosis.",
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AU - Suga, Shin Ichi

AU - Itoh, Hiroshi

AU - Komatsu, Yasato

AU - Ishida, Hiroshi

AU - Igaki, Toshio

AU - Yamashita, Jun

AU - Doi, Kentaro

AU - Chun, Tae Hwa

AU - Yoshimasa, Takaaki

AU - Tanaka, Issei

AU - Nakao, Kazuwa

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