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.

MATERIAL AND 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.

CONCLUSION:

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: Angela Storka, Bernhard Burian, Gerhard Führlinger, Breanna Clive, Terri Sun, Richard Crevenna, Andrea Gsur, Wilhelm Mosgöller, Michael Wolzt
• Journal: Journal of translational medicine (J Transl Med) Vol. 11 Pg. 117 (May 07 2013) ISSN: 1479-5876 [Electronic] England
• PMID: 23651810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
• Receptors, Vasoactive Intestinal Peptide, Type II
• Receptors, Vasoactive Intestinal Polypeptide, Type I

Topics

• Adolescent
• Adult
• Cell Separation
• Endotoxemia (metabolism)
• Escherichia coli (metabolism)
• Flow Cytometry
• Gene Expression Profiling
• Gene Expression Regulation
• Granulocytes (cytology)
• Humans
• Inflammation
• Leukocytes, Mononuclear (cytology)
• Lymphocytes (cytology)
• Male
• Middle Aged
• Monocytes (cytology)
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I (metabolism)
• Receptors, Vasoactive Intestinal Peptide, Type II (metabolism)
• Receptors, Vasoactive Intestinal Polypeptide, Type I (genetics, metabolism)
• Time Factors
• Young Adult