Relationship between lysosomal-associated membrane protein-2 and anti-phosphatidylserine/prothrombin complex antibody in the pathogenesis of cutaneous vasculitis.

Objectives: We investigated the relationship between lysosomal-associated membrane protein-2 (LAMP-2) and anti-phosphatidylserine/prothrombin (PS/PT) antibody in the pathogenesis of cutaneous vasculitis.

Methods: Cell surface LAMP-2 expression of human neutrophils was measured using flow cytometry. Twenty inbred wild-type Wistar-King-Aptekman-Hokudai (WKAH) rats were divided into four groups: Group 1, rabbit IgG injection only as negative control (n=5); Group 2, both histone and rabbit IgG injection (n=5); Group 3, anti-LAMP-2 antibody injection only (n=5); and Group 4, both histone and anti-LAMP-2 antibody injection (n=5). Ten WKAH rats were divided into two groups: Group A, histone, anti-PS/PT antibody, and anti-LAMP-2 antibody injection (n=5), and Group B, histone, anti-PS/PT antibody, and rabbit IgG injection as control (n=5).

Results: LAMP-2 expression on human neutrophils was induced by cell-free histone exposure in a dose- and time-dependent manner. Histopathological examination revealed the recruitment of neutrophils in cutaneous small vessels in all Group 4 rats. These observations were not evident in systemic organs other than the skin. LAMP-2 expression on the surface of vascular endothelial cells was evident in Group 2, exclusively in the skin, but not in Group 1. Thrombi were detected in various organs in all Groups A and B rats. However, no apparent thrombi were observed in the skin.

Conclusions: Anti-PS/PT and anti-LAMP-2 antibodies are responsible for independent effector mechanisms in the rats given intravenous injection of cell-free histones. We considered that undetermined factors other than cell-free histones could be required for the induction of cutaneous vasculitis by anti-PS/PT and anti-LAMP-2 antibodies.