Complement-mediated and direct activation of human neutrophils induced by

Introduction: Pararamosis is an occupational inflammatory disease caused by contact with hairs of the caterpillar Methods: Neutrophils isolated from healthy donors were directly stimulated with the extract or incubated with plasma derived from whole blood treated with the extract, in the presence or absence of compstatin, a C3 inhibitor that blocks complement activation, and PMX205, a selective C5aR1 antagonist applied directly to neutrophils. We assessed neutrophil activation by measuring cytokine and chemokine secretion, myeloperoxidase and elastase release, and neutrophil extracellular trap (NET) formation. Results: Our results reveal that pararama hair extract directly activates neutrophils, enhancing pro-inflammatory mediator release and degranulation. Moreover, plasma from extract-treated human whole blood samples further potentiated neutrophil activation, which was significantly reduced by compstatin, through inhibition of C3, and by selective blockade of the C5a receptor (C5aR1). Discussion: These findings highlight the integrated role of complement in neutrophil activation, as compstatin broadly inhibited complement-dependent effects, while PMX205 demonstrated the specific contribution of the C5a-C5aR1 axis. Targeting complement thus emerges as a promising strategy to mitigate inflammation and tissue damage in affected individuals.