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Type of publication: Baccalaureate Thesis
Type of document:

Year: 2010

Authors: Seper, Martin

Title: VPAC-Expressionsanalyse im humanen Entz├╝ndungsmodell.

Other title: Analysis of VPAC Expression in a human model of inflammation

Source: Bakkalaureatsarbeit, Vet. Med. Univ. Wien, pp. 36.


Advisor(s):

Wolzt Michael
Saalm├╝ller Armin

Reviewer(s):
Strasser Alois

Vetmed Research Units:
Institute of Immunology


Graduation date: 21.02.11


Abstract:
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are peptides of the secretin/glucagon family. VIP was first described in the small intestine as a molecule with a broad spectrum of functions in the organism. It does not only affect the gastro-intestinal system but it also shows systemic vasodilatation, bronchodilatation in the lungs and neurotrophic properties in the central nervous system. The International Union of Basic and Clinical Pharmacology (IUPHAR) defined 3 different receptors, namely the VPAC1, VPAC2 and PAC1 receptors with VIP and pituitary adenylate cyclase-activating polypeptide (PACAP) as their ligands. PACAP has a higher affinity to PAC1 than VIP. These G-protein coupled receptors were found in various tissues such as the nervous system, liver, lungs, pancreas, glands, smooth musculature, blood vessels and immune cells. The immune response is regulated by different sorts of cytokines and cells. VIP modulates the release of anti-inflammatory and pro-inflammatory molecules and has an effect on phagocytosis-activity, migration and differentiation of leukocytes. This demonstrates the potential role of VIP and its receptors as target of therapeutical attemps in treatment of acute, chronic and autoimmune diseases. Aim of this investigation was to show the regulation of VPAC receptors on human leukocytes in response to lipopolysaccharide administration. Blood samples of 20 healthy volunteers were taken before, 3, 6 and 24 hours after intravenous application of 2ng/kg bodyweight LPS. The blood was stained with polyclonal and monoclonal VPAC1, VPAC2 and PAC1 antibodies, the red blood cells were lysed and the receptor expression was determined by flow cytometry. The results had shown different kinds of VPAC expressions in lymphocytes, monocytes and granulocytes. Lymphocytes increased VPAC receptors on the cell surface during the acute inflammation and returned to normal levels 24 hours later. In contrast, VPAC receptors were down-regulated in phagocytes for the first 6 hours and increased the expression as recently as the inflammation was finished. After 24 hours, VPAC receptor-levels were normalized in granulocytes and up-regulated in monocytes. VPAC2 was specifically expressed in a biphasic way in monocytes during the inflammation. The down-regulation of VPAC in phagocytes under inflammatory conditions corresponds with earlier investigations and could be explained by receptor internalisation. The VPAC up-regulation on lymphocytes conflicts earlier in vitro studies. Further researches are required for a better understanding of the VPAC-regulation mechanisms.


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