C-type natriuretic peptide is synthesized and secreted from leukemia cell lines, peripheral blood cells, and peritoneal macrophages

Objective. C-type natriuretic peptide (CNP) is the third member of the natr iuretic peptide family, Cultured endothelial cells secrete CNP, and its sec retion rate from the endothelial cells is augmented by lipopolysaccharide, interleukin-1 beta, and tumor necrosis factor-alpha, which participate in t he pathophysiology of inflammation. In this study, we investigated the regu lation of CNP secretion from monocytes and macrophages to estimate its cont ribution to the progression of inflammation. Materials and Methods. CNP secretion rates from two human leukemia cell lin es (THP-1 and HL-60), human peripheral blood lymphocytes, granulocytes, mon ocytes, 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 radi oimmunoassay. Results. The secretion rates of CNP from THP-1 and HL-60 cells were augment ed according to the degree of their differentiation into macrophage-like ce lls under the stimulation with phorbol ester, Peripheral blood monocytes al so increased the CNP secretion rate after their differentiation into macrop hages, Retinoic acid elicited synergistic effects on the CNP secretion rate from HL-60 cells when administered with lipopolysaccharide, interferon-gam ma, interleukin-1 beta, tumor necrosis factor-alpha, or phorbol ester, In c ontrast, the phorbol ester-stimulated CNP secretion rate from THP-I cells w as suppressed with dexamethasone, which inhibits monocyte differentiation i nto macrophage. Conclusions. The secretion rate of CNP from monocytes was shown to be regul ated based on the degree of their differentiation. This study provides evid ence that the monocyte/macrophage system is one of the sources of CNP, espe cially under inflammatory conditions. (C) 2001 International Society for Ex perimental Hematology, Published by Elsevier Science Inc.