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.
Clinical Experiment Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China.
Ji-Fu
JF
Wei
Xiao-long
XL
Wei
Qiu-Yu
QY
Chen
Shao-Heng
SH
He
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