engleski

Serum levels of angiopoietins and Tie-2 in patients with leptospirosis or hemorrhagic fever with renal syndrome

Introduction Hemorrhagic fever with renal syndrome (HFRS) is caused by viruses of the genus Hantavirus, family Bunyaviridae, while spirochetes of the genus Leptospira provoke leptospirosis. The two zoonotic diseases are similar in their clinical picture and in severe cases may lead to hemorrhages, acute renal failure and mortality of 1 – 10%. It is shown that Tie-2 activation by angiopoietin-1 (Ang-1) inhibits apoptosis in endothelial cells, but the contradictory data about the angiopoietin-2 (Ang-2) are published. The aim of the study was to define possible interaction of Ang-1/Ang-2 and their receptor Tie-2 in patients infected with hantaviruses or leptospires. Methods We obtained sera samples from 35 HFRS patients, 11 patients with leptospirosis (including eight paired sera) and 14 controls (general population). Serology testing was done by ELISA test (HFRS) and microscopic agglutination test (MAT) -12 Leptospira interrogans serovars. All sera were tested by ELISA tests for Ang-1, Ang-2 and Tie-2 according to the manufacturer’ s protocol (R&D Systems, Minneapolis, MN, USA). Nonparametric statistical analysis was used. Results In acute (p<0.05) and paired (p<0.05) sera of patients with leptospirosis significantly decreased serum levels of Tie-2 were detected. No differences in comparison to the controls were observed in HFRS patients. In contrast, Ang-1 levels were higher in HFRS patients than in healthy controls, while no differences were found between controls and patients with leptospirosis. No significant differences were observed with Ang-2. HFRS patients were infected mostly by Puumala virus (mild to moderate diseases). Leptospira antibodies in titres ranged 100 to 16, 000 were found for all 12 serovars. Conclusions The interruption of Tie-2 signaling may lead to loss of endothelial cell viability. So far there is no published data that leptospires induce apoptosis in endothelial cells. There is some evidence about binding of leptospiral antigens to capillary endothelial cells. Peptidoglycans from pathogenic leptospires are among the molecules that can directly activate vascular endothelial cells to increase their adhesiveness for neutrophilic granulocytes. Increase of Ang-1 in sera of HFRS patients may represent an attempt for the protection of endothelial cells from apoptosis induced by hantaviruses. There is still lack of evidence about mechanisms of apoptosis in HFRS and leptospirosis.

HFRS; leptospirosis

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