Complement System Inhibition Modulates the Inflammation Induced by the Venom of Premolis semirufa, an Amazon Rainforest Moth Caterpillar

Abstract

The caterpillar of the Premolis semirufa moth, commonly called Pararama, is found in the Brazilian Amazon region. Contact with the hairs can cause a chronic inflammatory reaction, termed “pararamosis”. To date, there is still no specific treatment for pararamosis. In this study, we used a whole human blood model to evaluate the involvement of the complement in the proinflammatory effects of P. semirufa hair extract, as well as the anti-inflammatory potential of complement inhibitors in this process. After treatment of blood samples with the P. semirufa hair extract, there was a significant increase in the generation of soluble terminal complement complex (sTCC) and anaphylatoxins (C3a, C4a, and C5a), as well as the production of the cytokines TNF-α and IL-17 and the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10. The inhibition of C3 with compstatin significantly decreased IL-17, IL-8, RANTES, and MCP-1 production. However, the use of the C5aR1 antagonist PMX205 promoted a reduction in the production of IL-8 and RANTES. Moreover, compstatin decreased CD11b, C5aR1, and TLR2 expression induced by P. semirufa hair extract in granulocytes and CD11b, TLR4, and TLR2 in monocytes. When we incubated vascular endothelial cells with extract-treated human plasma, there was an increase in IL-8 and MCP-1 production, and compstatin was able to decrease the production of these chemokines. C5aR1 antagonism also decreased the production of MCP-1 in endothelial cells. Thus, these results indicate that the extract of the Pararama bristles activates the complement system and that this action contributes to the production of cytokines and chemokines, modulation of the expression of surface markers in leukocytes, and activation of endothelial cells.

Occupational Exposure of Forest Workers to the Urticating Setae of the Pine Processionary Moth Thaumetopoea pityocampa

“…(Lasiocampidae) in China and Siberia, when the workers remove the cocoons by hand from the branches as part of pest control actions and come in contact with the modified setae embedded by the larvae in the cocoon [ 25 ]. In another case, the rubber extractors in Brazil may accidentally come in contact with the caterpillar hairs of Premolis semirufa (Erebidae) when they extract the latex [ 26 ]. In our study, the exposure of the chainsaw operators was indirect, as the larvae dispersed the setae in the habitat, and the workers did not report any direct contact with the larvae or the nests.…”

Complement System Inhibitory Drugs in a Zebrafish (Danio rerio) Model: Computational Modeling

“…PMX205 (N(2)-(3-phenylpropanoyl)-L-Orn-L-Pro-3-D-Cha-L-Trp-L-Arg) is a peptide antagonist to C5aR1. This molecule has been used as a pharmacological tool and therapeutic agent in experimental models for inflammatory diseases, including amyotrophic lateral sclerosis [ 43 ], colitis [ 44 ], meningococcal meningitis [ 45 ], Alzheimer’s disease [ 46 ], envenomation [ 38 , 47 ] and periodontitis [ 48 ].…”

Molecular Mechanisms of Animal Toxins, Venoms and Antivenoms

“…The immune system is also influenced by these toxins; for example, complement is depleted by the cobra venom factor [4]. The manuscripts submitted to this Special Issue uncover the molecular mechanisms of animal toxin effects on the cardiovascular [5] and immune [6] systems.…”