title: VPAC1 receptor expression in peripheral blood mononuclear cells in a human endotoxemia model.
abstract: BACKGROUND
  Vasoactive intestinal peptide (VIP) exerts immune-modulatory actions mainly via VPAC1 receptor stimulation. VPAC1 may be a treatment target of inflammatory diseases, but little is known about the receptor expression profile in immune-competent cells in vivo.
  
  
  METHODS
  20 male healthy subjects received a single intravenous bolus of 2 ng/kg body weight Escherichia coli endotoxin (LPS). Receptor status was evaluated in peripherial blood cells before and 3, 6 and 24 h after LPS by FACS analysis and q-PCR. VIP plasma concentrations were measured by ELISA.
  
  
  RESULTS
  Granulocytes accounted for 51% of leukocytes at baseline and 58 ± 37% were positive for VPAC1. The granulocyte population increased 2.6 fold after LPS, and a transient down-regulation of VPAC1 to 28 ± 23% was noted at 3 h (p < 0.001), which returned to baseline at 24 hours. Baseline VPAC1 expression was low in lymphocytes (6.3 ± 3.2%) and monocytes (11 ± 9.6%). In these cells, LPS up-regulated VPAC1 at 6 h (13.2 ± 4.9%, p < 0.001) and 24 h (31.6 ± 20.5%, p = 0.001), respectively. Consistent changes were noted for the VIP-receptors VPAC2 and PAC1. VPAC1, VPAC2 and PAC1 mRNA levels were unchanged in peripheral blood mononuclear cells (PBMC). VIP plasma concentration increased from 0.5 ± 0.3 ng/ml to 0.7 ± 0.4 ng/ml at 6 h after LPS (p < 0.05) and returned to baseline within 24 h.
  
  
  CONCLUSIONS
  The time profile of VPAC receptor expression differs in granulocytes, monocytes and lymphocytes after LPS challenge in humans. Changes in circulating VIP concentrations may reflect innate immune responses.
authors: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, 1090, Austria.
authors: Angela
authors: A
authors: Storka
authors: Bernhard
authors: B
authors: Burian
authors: Gerhard
authors: G
authors: Führlinger
authors: Breanna
authors: B
authors: Clive
authors: Terri
authors: T
authors: Sun
authors: Richard
authors: R
authors: Crevenna
authors: Andrea
authors: A
authors: Gsur
authors: Wilhelm
authors: W
authors: Mosgöller
authors: Michael
authors: M
authors: Wolzt
mesh_terms: D000293:Adolescent; D000328:Adult; D002469:Cell Separation; D019446:Endotoxemia / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult
chemical_list: D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I
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