Neutralization of dermonecrotic and lethal activities and differences among 32-35 kDa toxins of medically important Loxosceles spider venoms in Brazil revealed by monoclonal antibodies

Neutralization of dermonecrotic and lethal activities and differences among the principal toxic proteins (32-35 kDa) of medically important Loxosceles spider venoms in Brazil (Loxosceles gaucho, Loxosceles laeta and Loxoscele s intermedia) were studied using monoclonal antibodies (MAbs) produced agai nst the dermonecrotic component (35 kDa) of L, gaucho venom. MAb titers wer e 512,000 to homologous venom, between 2000 and 64,000 for L. intermedia ve nom and between 1000 and 64,000 fort. laeta venom. By Western blotting, MAb s could recognize mainly the 35 kDa protein of L. gaucho venom and with les s intensity the 35 kDa protein of L. intermedia venom. These MAbs also reco gnized weakly or did not recognize the 32 kDa component of L. laeta venom. Only MoALg(1) showed high affinity for L. gaucho venom and neutralized in v ivo 90-97% of the dermonecrotic activity, besides delaying the lethality in duced by homologous venom. MoALg(1) maintained its capacity to neutralize t he dermonecrotic activity, even when administered (i.v.)6 h after envenomin g (i.d.). All MAbs obtained failed to neutralize the toxic activities of th e heterologous venoms. These results suggest that different epitopes are present in the protein re sponsible for the dermonecrotic activity of Loxosceles venoms, and confirm the participation of other venom components during the local reaction proce ss. This study also confirms the importance of antibodies for neutralizatio n of dermonecrotic activity, even when administered some hours after enveno ming, and emphasizes the differences of composition and toxicity of medical ly important Loxosceles venoms. These findings must be considered in order to improve loxoscelism immunotherapy. (C) 2001 Elsevier Science Ltd. All ri ghts reserved.