Endothelins, peptides with potent vasoactive properties, are produced by human macrophages.

Abstract

SummaryEndothelins are peptides, originally isolated from endothelial cells, with potent vasoactive and mitogenic properties. In this study, we demonstrate that human macrophages synthesize and secrete endothelins . Cultured human macrophages were found by immunocytochemistry to stain positively for endothelin 1 and endothelin 3. Their capability to produce and release these peptides was confirmed by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassays, specific for endothelin 1 and 3, respectively. Immunoreactive peptides were identified both in cellular extracts and in macrophage-conditioned medium. The secretion of endothelin 1, but not of endothelin 3, from macrophages could be stimulated 6-10-fold by lipopolysaccharide or phorbol myristate acetate (PMA). Northern blot analysis oftotal macrophage RNA using an endothelin 1 cDNA probe revealed induction of endothelin mRNA in PMA treated macrophages . Furthermore, immunoreactive endothelin 1 and 3 were found in U937 cells, a human promonocytic line, and in freshly isolated human monocytes . In contrast, no immunoreactive endothelin was detected in cell extracts from human neutrophils and lymphocytes . The expression of endothelins in tissue macrophages was demonstrated in paraffin sections of human lung using immunohistochemistry. In conclusion, the finding that human macrophages produce endothelins suggests an important role for these peptides in the microenvironment of tissue macrophages . Macrophage-derived endothelins may have an essential function in blood vessel physiology, and aberrant production may contribute to vessel pathology.

Endothelin-1 in stable bronchiectasis

“…It is therefore likely that the high levels of ET-1 detected in P. aeruginosa-infected patients genuinely reflects an up-regulation of ET-1 expression by P. aeruginosa infection. Other bacterial products such as Escherichia coli lipolysaccharide and pro-inflammatory cytokines, such as IL-1b and TNFa also up-regulate ET-1 expression in human bronchial epithelium [6]. Migration of neutrophils from the intravascular compartment to an inflammed tissue requires interaction of neutrophils with vascular endothelium and the presence of chemoattractants which serve as homing triggers.…”

“…2). Sputum leukocyte density was higher in P. aeruginosa-infected (median 48.7, interquartile range 15.7±97.7310 6 . mL -1 ) than in non-P. aeruginosa-infected patients (9.1, 1.5±25.5310 6 .…”

Modified low density lipoproteins activate human macrophages to secrete immunoreactive endothelin

“…The ability of human macrophages to secrete ET,.1 has been recently documented [8]. This publication has reported that PMA.…”

“…At the end of the attachment period the medium was rcplaccd with MEM supplcmcntcd with IO% FCS for the rest of the cxperimcnts. Cells were used hc!wccn day 15 and 20 after seeding [8]. For each cxpcriment (rr=3).…”

“…There is now evidence that Ox-LDLs induct the secretion of ET-l by endothelial cells [6] and that acetylated-LDLs (AC-LDLs) induce the secretion cf TNF by Abhre,'iu/iofr.v macrophages [7] via the scavenger receptors. On the other hand, it has been recently published that ET-l is produced by human macrophages stimulated with phorbol myristate acetate (PMA) [8]. On these grounds, we hypothesized that LDLs may trigger ET production by macrophages.…”