Trimeresurus flavoviridis (habu snake) venom induces human erythrocyte lysis through enzymatic lipolysis, complement activation and decreased membrane expression of CD55 and CD59.
Trimeresurus flavoviridis (habu snake) bites can be fatal to man because of its virulent venom, which is clinicopathologically classified as haemorrhagic, necrotic, and haemolytic toxins. Trimeresurus flavoviridis venom causes lysis of human erythrocytes in conditions where plasma is present as well as in plasma-free conditions in a dose-dependent manner. The haemolytic process requires Ca2+ and Mg2+ ions in the solution. Additionally, the venom initiates activation of the human complement cascade as evidenced by C3a and C5a releases, complement consumption indicated by CH50 and formation of soluble membrane attack complex. The insertion of membrane attack complex into the erythrocyte membranes is morphologically identified by electronmicroscopy. Immunofluorescence analysis reveals that incubation of erythrocytes with the venom decreased cell-surface expression of CD55 (decay accelerating factor) and CD59 (protectin), which renders erythrocyte more vulnerable to adherent C3 and C5 convertases and to polymerization of C9 into membranes, and may enhance autologous complement-mediated haemolysis triggered by the venom. Our data demonstrate that Trimeresurus flavoviridis venom induces haemolysis in the presence of plasma by three distinct mechanisms, direct lipolysis through PLA2 activity, activation of the human complement system, and cleavages of CD55 and CD59 from erythrocyte membranes.
Yamamoto
C
C
Faculty of Engineering, Sojo University, Ikeda, Kumamoto, Japan. yamamoto@nephro.ne.jp
Tsuru
D
D
Oda-Ueda
N
N
Ohno
M
M
Hattori
S
S
Kim
S T
ST
D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism*; D018957:CD59 Antigens / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology; D003435:Crotalid Venoms / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006461:Hemolysis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008066:Lipolysis / Q000187:drug effects* / Q000502:physiology; D017841:Trimeresurus
D018958:CD55 Antigens; D018957:CD59 Antigens; D003435:Crotalid Venoms