Expression of ICAM-1 on the Hantaan virus-infected human umbilical vein endothelial cells

OBJECTIVES: In HFRS, there is a varying degree of disseminated intravascular coagulation which was evident in the early phase of the illness. It is believed also that DIC would be the consequence, at least in part, of functional changes of endothelium resulting in kinin activation and clinical syndrome. This study investigated the role of adhesion molecule in the pathogenesis of Hantaan virus-related disease. METHODS: The expression of ICAM-1 antigen on the cell membrane of human umbilical vein endothelial cells was assessed by immunohistochemistry, and ICAM-1 mRNA in the endothelial cells was assessed by in situ hybridization after Hantaan virus infection (2.6 x 10(4) PFU/mL) with the time course. RESULTS: In immunohistochemistry, the number of ICAM-1 positive cells increased with time during the 12 or 24 hours after infection. 5 to 10% of HUVECs had been positive after 12-24 hours and the number of positive cells decreased abruptly after 24 hours. Hantaan antigen had been noticed after 12 hours focally on the HUVECs but continued to proliferate into day 7 post-infection when most of HUVECs were infected by Hantaan virus. In situ hybridization showed identical patterns of ICAM-1 mRNA expression after Hantaan virus infection. CONCLUSION: It implies that the Hantaan virus infection on HUVECs would express more ICAM-1 on their surface and implicated in the pathogenesis of early clinical syndrome of HFRS.

Serum and urine soluble HLA class I antigen concentrations are increased in patients with hemorrhagic fever with renal syndrome

OBJECTIVES: In order to evaluate the association between the Hantaan virus-induced cellular-immune response and clinical severity in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We serially measured the serum (n = 16) and urine (n = 6) concentrations of soluble HLA class 1 antigen (sHLA-l) and clinical powameters in patients with HFRS. RESULTS: Serum sHLA-I concentrations in patients with HFRS were significantly higher than those in controls throughout all clinical phases (p < 0.01). The highly elevated Serum sHLA-I concentrations peaked in the oliguric phase and declined gradually through the phases of HFRS. Serum sHLA-l concentrations in patients with hypotensive episode were higher than in those without the episode (5,85 +/-2,184 vs. 2,389 +/- 860 ng/ml in oliguric phase, 4.11 +/- 1,952 vs. 1,502 +/- 592 ng/ml in diuretic phase, p < 0.05), and serum sHLA-l levels showed a significant correlation with blood WBC count (r = 0.75 in the febrile and hypotensive phase, p < 0.01) and serum creatinine concentrations (r = 0.64 in the oliguric phase, p< 0.01), respectively, Urine sHLA-I levels in the oliguric phase were significantly higher than those in the diuretic phase (390 +/- 155 vs. 214 +/- 45 ng/mg Cr, p < 0.05) and urine sHLA-I levels are associated with severe illness in patients with HFRS. The higher serum sHLA-I are associated with severe illness in patients with HFRS. The persistent elevation of serum sHLA-I during all phases of HFRS might be related to increased production due to prolonged cellular immunologic stimulation by the Hantaan virus rather than decreased excretion of sHLA-I through the kidney. CONCLUSION: We suggest that the serum and urine sHLA-I concentrations can be used as a stable and objective parameter for monitoring clinical severity and renal dysfunction in patients with HFRS.