Complement system is activated in acute inflammatory response to environmental particulates in the lungs

Abstract

Short-term exposure (typically ranging from a few hours to 7 days) to particulate matter (PM) elicits acute inflammatory responses with significant activation of complement component C5. However, the relationship between PM-induced complement system activation, acute inflammation, and the contributing factors remains unclear. In this study, we aimed to investigate the intensity of acute inflammatory responses, as well as the activation levels of complement C5 and its related products, C5aR1 and C5b-9, following exposure to different types of PM. Acute inflammatory responses and complement activation were assessed in mice intratracheally administered four types of PM: titanium dioxide (TiO₂), diesel exhaust particles (DEP), Asian sand dust (ASD), and ambient PM with an aerodynamic diameter ≤ 2.5 μm (PM2.5). Complement system and inflammatory markers were evaluated by analyzing increased C5 protein levels, C5b-9 deposition, and C5aR1 expression. Additionally, dark-field microscopy and Raman microscopy were used to detect PM components adjacent to infiltrating neutrophils, and elemental composition was quantified using ICP-MS and EDXRF. ASD, DEP, and PM2.5 exposure significantly increased C5b-9 deposition in lung tissues. All PM-exposed groups exhibited substantial upregulation of C5aR1 expression, primarily in neutrophils. Raman spectroscopic analysis revealed Si, K, Mg, Al, and Fe adjacent to infiltrating neutrophils in ASD-exposed lungs. Furthermore, elemental analysis identified Si, Mg, Al, and K as the most potent contributors to complement activation and inflammatory responses. Of the four types of PM, ASD induced the most severe acute inflammatory response and complement system activation. Therefore, ASD-induced complement system activation, driven at least partly by its mineral components, may play a critical role in neutrophil activation and acute pulmonary inflammation. These findings highlight the differential impact of PM types on complement system activation and underscore the importance of PM composition in the evaluation of air pollution-related health risks, particularly acute pulmonary inflammation.