title: Endothelin-1 production by the canine macrophage cell line DH82: enhanced production in response to microbial challenge.
abstract: Endothelin-1 (ET-1) is a potent vasoconstrictive peptide which plays an important role in regulating mammalian cardiovascular development and homeostasis. Originally identified as a factor released by vascular endothelial cells, ET-1 is now recognized as a product of numerous cells and tissues with demonstrated involvement in an array of physiological and pathological processes. An area of great interest is the production of ET-1 by mononuclear cells (monocytes and macrophages) and its role in inflammation. We report that the canine macrophage cell line, DH82, constitutively secretes both ET-1 and its biologically inactive precursor big ET-1. The production of both peptides was increased following stimulation with lipopolysaccharide (endotoxin) from gram-negative bacteria. ET-1 production was also increased in response to stimulation with intact and viable gram-positive and gram-negative bacteria. In addition to producing ET-1, DH82 cells express transcripts encoding two receptors for the ET-1 peptide (ET(A) and ET(B) receptors) and an enzyme involved in the conversion of big ET-1 to ET-1. The constitutive secretion of ET-1 and the expression of ET(A) and ET(B) receptors may be related to the malignant origin of this cell line. Our results are the first report of ET-1 production by a canine cell line and provide the basis for further investigation into the role of ET-1 during infection and inflammation.
authors.affiliation: Department of Microbiology and Immunology, Des Moines University, College of Osteopathic Medicine, 3200 Grand Ave., Des Moines, IA 50312, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Divino
authors.forename: Kashmira S
authors.initials: KS
authors.lastname: Chawla
authors.forename: Christina M
authors.initials: CM
authors.lastname: da Silva
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Bjorge
authors.forename: Andrew
authors.initials: A
authors.lastname: Brittingham
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D000072396:Endothelin-Converting Enzymes; D004926:Escherichia coli / Q000472:pathogenicity; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000472:pathogenicity
chemical_list: D017931:DNA Primers; D019332:Endothelin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes