Accidents involving multiple bee stings have been frequently reported in warm climate regions, specially South and Central America and south United States. Attacks of affricanized bees can cause systemic reactions and even be lethal in a susceptible person. Coagulation abnormality is a rarer complication, but hemolisys, bleeding, thrombocytopenia and disseminated intravascular coagulation had been reported. Some of these symptoms were already associated to high concentrations of venom and phospholipase A2 (PLA2) in serum and urine of patients. However, besides PLA2 being the major enzyme component in bee venom, about 50% of the crude venom dry weight is composed by melittin. Melittin is a well characterized hemolytic peptide of 26 aminoacids from Apis mellifera venom with the ability of pore formation in membranes. It is also known that the peptide has a modulatory effect over certain proteins, especially phospholipases. In order to determine the role of melittin in coagulation disorders produced by bee sting, here we show the effect of the peptide in platelet aggregation and some coagulation parameters.
Platelet aggregation assays were performed both in platelets rich plasma (PRP) and washed rabbit platelets (WRP). The coagulation parameters were assessed by APTT, PT, recalcification time and fibrinocoagulation. A direct comparison of these effects and the ones induced by crude bee venom and PLA2 was also performed.
Melittin was able to induce platelet aggregation in a dose-dependent manner, in the same fashion as crude venom and in opposite way of phospholipase A2. It was observed a delay in recalcification time in low peptide concentration (from 170 ng/mL), as well as a reduction in APTT. The overall anticoagulant effect of melittin can be associated in vivo to the effect of PLA2 and the bleeding disorders.
These findings could be useful not only for the identification of coagulation abnormalities in patients who suffer bee attack, but also in the study of the mechanism by which melittin affects hemostasis. Identification of novel proteins modulated by melittin could give an insight in the development of new peptide-like drugs for the treatment of coagulation disorders.
Supported by CAPES and CNPq