Deleted in Malignant Brain Tumors 1 is up-regulated in bacterial endocarditis and binds to components of vegetations.

OBJECTIVE

Bacterial endocarditis is a frequent infectious cardiac disease, especially in patients with congenital or acquired heart defects. It is characterized by bacterial colonization of the heart valves and the appearance of vegetations consisting of fibrin, blood cells, and bacteria. The glycoprotein Deleted in Malignant Brain Tumors 1 is a scavenger receptor cysteine-rich protein with functions in innate immunity and epithelial differentiation. Because of the aggregating capacity of Deleted in Malignant Brain Tumors 1, we hypothesized that an up-regulation in bacterial endocarditis may be linked to the development of vegetations.

METHODS

Heart tissue of 19 patients with bacterial endocarditis and 10 controls without bacterial endocarditis was analyzed by immunohistochemistry. The effect of human recombinant Deleted in Malignant Brain Tumors 1 on erythrocyte aggregation was measured using an automated red blood cell aggregometer MA1. Binding of human recombinant Deleted in Malignant Brain Tumors 1 to erythrocyte membranes, platelets, fibrin, and fibrinogen was analyzed by Western blotting and enzyme-linked immunosorbent assay.

RESULTS

Deleted in Malignant Brain Tumors 1 expression was up-regulated in affected heart valves with bacterial endocarditis and limited to the colonizing bacteria on the heart valves and granulocyte-depleted fibrin/fibrinogen formations, and around localized atheromatosis. Patients with aggressive bacteria showed higher DMBT1 levels than patients with less aggressive bacteria. Human recombinant Deleted in Malignant Brain Tumors 1 aggregates erythrocytes and binds to erythrocyte membranes, platelets, and fibrin/fibrinogen.

CONCLUSION

Deleted in Malignant Brain Tumors 1 up-regulation at sites of bacterial endocarditis, its association with platelets and fibrin/fibrinogen, and its ability to aggregate erythrocytes through binding to their membranes indicate a potential role in the development of vegetations and thrombosis.