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C-type natriuretic peptide is synthesized and secreted from leukemia cell lines, peripheral blood cells, and
1National Cardiovascular Center Research Institute, Osaka, Japan.
Insights
C-type natriuretic peptide (CNP) secretion from monocytes and macrophages is regulated by cell differentiation. This study identifies the monocyte/macrophage system as a key source of CNP, particularly during inflammation.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- C-type natriuretic peptide (CNP) is a natriuretic peptide family member secreted by endothelial cells.
- CNP secretion is influenced by inflammatory mediators like lipopolysaccharide (LPS), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α).
Purpose of the Study:
- To investigate the regulation of CNP secretion from monocytes and macrophages.
- To assess the contribution of the monocyte/macrophage system to inflammation.
Main Methods:
- Measured CNP secretion rates from human leukemia cell lines (THP-1, HL-60), peripheral blood cells (lymphocytes, granulocytes, monocytes), and macrophages.
- Utilized radioimmunoassay to quantify immunoreactive CNP levels in cell culture media.
- Investigated effects of differentiation stimuli (phorbol ester, retinoic acid) and inflammatory mediators.
Main Results:
- CNP secretion increased with differentiation of THP-1 and HL-60 cells into macrophage-like cells.
- Monocyte differentiation into macrophages augmented CNP secretion.
- Retinoic acid synergistically enhanced CNP secretion with inflammatory stimuli in HL-60 cells.
- Dexamethasone suppressed CNP secretion in phorbol ester-stimulated THP-1 cells.
Conclusions:
- Monocyte CNP secretion is regulated by differentiation status.
- The monocyte/macrophage system is a significant source of CNP, especially in inflammatory contexts.
Objective:
C-type natriuretic peptide (CNP) is the third member of the natriuretic peptide family. Cultured endothelial cells secrete CNP, and its secretion rate from the endothelial cells is augmented by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha, which participate in the pathophysiology of inflammation. In this study, we investigated the regulation of CNP secretion from monocytes and macrophages to estimate its contribution to the progression of inflammation.
Materials And Methods:
CNP secretion rates from two human leukemia cell lines (THP-1 and HL-60), human peripheral blood lymphocytes, granulocytes, monocytes, monocyte-derived macrophages, and mouse peritoneal macrophages were measured under conditions with or without stimulation. Immunoreactive CNP levels in the culture media of these cells were measured by a specific radioimmunoassay.
Results:
The secretion rates of CNP from THP-1 and HL-60 cells were augmented according to the degree of their differentiation into macrophage-like cells under the stimulation with phorbol ester. Peripheral blood monocytes also increased the CNP secretion rate after their differentiation into macrophages. Retinoic acid elicited synergistic effects on the CNP secretion rate from HL-60 cells when administered with lipopolysaccharide, interferon-gamma, interleukin-1beta, tumor necrosis factor-alpha, or phorbol ester. In contrast, the phorbol ester-stimulated CNP secretion rate from THP-1 cells was suppressed with dexamethasone, which inhibits monocyte differentiation into macrophage.
Conclusions:
The secretion rate of CNP from monocytes was shown to be regulated based on the degree of their differentiation. This study provides evidence that the monocyte/macrophage system is one of the sources of CNP, especially under inflammatory conditions.