title: Vasoactive intestinal peptide (VIP) receptor expression in monocyte-derived macrophages from COPD patients.
abstract: Vasoactive intestinal peptide (VIP) is one of the most abundant molecules found in the respiratory tract. Due to its anti-inflammatory and bronchodilatatory properties, it has been proposed as a novel treatment for chronic obstructive pulmonary disease (COPD). The actions of VIP are mediated via three different G-protein-coupled receptors (VPAC1, VPAC2 and PAC1) which are expressed in the respiratory tract and on immunocompetent cells including macrophages. Alveolar macrophages (AM) are key players in the pathogenesis of COPD and contribute to the severity and progression of the disease. While VPAC1 has been reported to be elevated in subepithelial cells in smokers with chronic bronchitis, little is known about VPAC expression of AM in COPD patients. AM from COPD patients show a strong VPAC1 expression which exceeds VPAC2. A similar receptor expression pattern was also observed in lipopolysaccharide (LPS)-activated monocyte-derived macrophages (MDM) from healthy volunteers and COPD patients. VIP has been shown to down-regulate interleukin 8 (IL-8) secretion significantly in MDM after LPS stimulation. The response to VIP was similar in MDM from COPD patients and healthy volunteers. Our results indicate that VPAC1 up-regulation in macrophages is a common mechanism in response to acute and chronic pro-inflammatory stimuli. Although VPAC1 up-regulation is dominant, both receptor subtypes are necessary for optimal anti-inflammatory signaling. The high VPAC1 expression in AM may reflect the chronic pro-inflammatory environment found in the lung of COPD patients. Treatment with VIP may help to decrease the chronic inflammation in the lung of COPD patients.
authors.affiliation: Medical University of Vienna, Department of Internal Medicine II, Division of Pulmonary Medicine, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Burian
authors.forename: Angela
authors.initials: A
authors.lastname: Storka
authors.forename: Beatrice A
authors.initials: BA
authors.lastname: Marzluf
authors.forename: Yong-Cheng
authors.initials: YC
authors.lastname: Yen
authors.forename: Christopher
authors.initials: C
authors.lastname: Lambers
authors.forename: Bruno
authors.initials: B
authors.lastname: Robibaro
authors.forename: Karin
authors.initials: K
authors.lastname: Vonbank
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Mosgoeller
authors.forename: Ventzislav
authors.initials: V
authors.lastname: Petkov
mesh_terms: D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics / Q000276:immunology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000276:immunology*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I