HK antibodies block Aβ42-induced HK cleavage and bradykinin release in human plasma. (A) Representative transmission electron microscopy image of Aβ42 used in this study. (Scale bar, 500 nM.) (B) HK Western blot shows that, in the absence of HK antibodies, Aβ42 completely cleaved HK. However, the 3E8 HK antibody dose-dependently blocked Aβ42-induced HK cleavage. The 2B7 antibody (at 0.1 and 0.5 μM) also showed a limited protective effect against HK cleavage. The 4B12 HK antibody and control IgG did not show any effects on HK cleavage. (C) The protective effects of 3E8 HK antibody were quantified as described in Fig. 1. The 3E8 antibody dose-dependently blocked Aβ42-induced HK cleavage, and, at 0.5 μM, it completely blocked HK cleavage. Control IgG did not show any effect on HK cleavage. (D) The effects of 3E8 antibody on Aβ42-induced bradykinin production were measured by bradykinin ELISA. Aβ42 induced a dramatic increase in bradykinin production, but the addition of 3E8 (0.5 μM) completely blocked Aβ42’s effects on bradykinin generation. The 3E8 at 0.02 or 0.1 μM also significantly blocked bradykinin production. Control IgG did not show any effects on Aβ42-induced bradykinin production. Data are denoted as mean ± SD. **P ≤ 0.01, ***P ≤ 0.001. P > 0.05 was not significant (n.s.).