Fig. 9

Proposed airway macrophage response to pre- and post-incinerated nanoclay particles in the A presence or B absence of lipid polysaccharide and its role in pulmonary fibrosis AOP. With LPS co-stimulation, uncoated nanoclay (NC) exposure caused a robust inflammatory response (KE1) and apoptosis while ONC exposure caused membrane damage, pyroptosis, and an acute T_H2 inflammation (KE1) signal. Incinerated nanoclay exposure resulted in apoptosis, minimal inflammatory (I-ONC), or a relatively benign (I-NC) response. In a sterile exposure model uncoated NC and ONC exposure caused DAMP release (MIE), mitochondrial membrane depolarization and cell lysis, respectively, along with a mixed T_H1/T_H2/T_H17 pro-inflammatory response (KE1). Incinerated nanoclay exposure collectively produced an acute mixed T_H1/T_H2/T_H17 inflammatory response. These findings for pre-incinerated nanoclays aligned with increased inflammatory cell recruitment in the in vivo model (KE2)