Yeungnam Univ J Med.  2008 Jun;25(1):41-49.

The Effects of Hantaan Virus on the Expression of Platelet Activating Factor Receptor and on the Activity of Platelet Activating Factor Acetylhydrolase

• Hwang JY
• Park JW
• Hong SY
• Park HS

Abstract

BACKGROUND: The central physiological derangement of hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) is a vascular dysfunction, manifested by hemorrhage, impaired vascular tone and increased vascular permeability. Platelet activating factor (PAF), whose actions are mediated through a specific receptor, is a potent bioactive lipid. PAF has diverse biological functions in the vascular system, such as increasing vascular permeability, adhesion of leukocytes to the endothelium and reduction of cardiac output, which result in hypotension and shock. The goal of the present study was to investigate whether PAF is involved in the pathogenesis of HFRS. For this purpose, we evaluated the effect of HTNV on the expression of PAF receptor (PAF-R) and on the activity of PAF-acetylhydrolase (PAF-AH) instead of PAF because PAF is rapidly degraded by PAF-AH in vivo.
MATERIALS AND METHODS
To evaluate the expression of PAF-R, we performed reverse-transcription PCR, western blot and FACS analyses using HTNV-infected human umbilical vein endothelial cells (HUVECs) and non-infected (control) HUVECs. In addition, we measured the activity of plasma PAF-AH in HFRS patients and normal healthy persons.
RESULTS
The mRNA and protein expression of PAF-R was increased in HTNV-infected HUVECs compared with control HUVECs at 2 and 3 days post-infection (d.p.i.). FACS analysis showed that HTNV induced the surface expression of PAF-R in HUVECs from 2 d.p.i. The activity of plasma PAF-AH was 2.5-fold lower in HFRS patients than in normal healthy persons.
CONCLUSION
Increased PAF-R expression by HTNV might increase the responsiveness to PAF in endothelial cells. Reduced PAF-AH activity in the blood of HFRS patients might delay PAF degradation. These results suggest that changes in PAF-R and PAF-AH by HTNV might influence to PAF activity and might be involved in the vascular dysfunction of HFRS.

Keyword

HFRS; Platelet activating factor; PAF receptor; PAF-acetylhydrolase

MeSH Terms

Blood Platelets
Blotting, Western
Capillary Permeability
Cardiac Output
Endothelial Cells
Endothelium
Hantaan virus
Hemorrhage
Hemorrhagic Fever with Renal Syndrome
Human Umbilical Vein Endothelial Cells
Humans
Hypotension
Leukocytes
Plasma
Platelet Activating Factor
Platelet Membrane Glycoproteins
Polymerase Chain Reaction
Receptors, G-Protein-Coupled
RNA, Messenger
Shock
Platelet Activating Factor
Platelet Membrane Glycoproteins
RNA, Messenger
Receptors, G-Protein-Coupled