Induction of inflammatory cell accumulation by TM-N49 and promutoxin, two novel phospholipase A(2).
Local inflammation is a prominent characteristic of snakebite wound. Snake venom phospholipase A(2)s (PLA(2)s) are one of the main components which contribute to accumulation of inflammatory cells. We have isolated TM-N49 and promutoxin from Protobothrops mucrosquamatus venom and investigated their ability in induction of cell accumulation by using an in vivo mouse model. The results showed that both TM-N49 and promutoxin are potent stimuli for induction of neutrophil, lymphocyte, macrophage and eosinophil accumulation in the mouse peritoneum. The TM-N49- and promutoxin-induced inflammatory cell accumulation was inhibited by pretreatment of animals with cyproheptadine, terfenadine and Ginkgolide B, indicating that histamine and PAF is likely to contribute to the cells accumulation. Pre-injection of antibodies against adhesion molecules ICAM-1, CD18, CD11a and L-selectin showed that ICAM-1 is a key adhesion molecule of TM-N49- and promutoxin-induced lymphocyte, macrophage and eosinophil accumulation; CD18 and CD11a plays an important role in the migration of neutrophils, eosinophils and macrophages; and L-selectin is involved in the neutrophil and eosinophil accumulation. In conclusion, induction of inflammatory cell accumulation by TM-N49 and promutoxin confirms that group II PLA(2)s is pivotal stimulus for cell infiltration, through which they participate in the formation of snakebite inflammation.
Wei
Ji-Fu
JF
Clinical Experiment Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China.
Wei
Xiao-long
XL
Chen
Qiu-Yu
QY
He
Shao-Heng
SH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D003435:Crotalid Venoms / Q000201:enzymology*; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D054501:Group II Phospholipases A2 / Q000302:isolation & purification / Q000633:toxicity*; D007111:Immunity, Cellular / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D030162:Reptilian Proteins / Q000302:isolation & purification / Q000633:toxicity*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D003435:Crotalid Venoms; D030162:Reptilian Proteins; D054501:Group II Phospholipases A2; C510097:TM-N49 protein, Protobothrops mucrosquamatus