Figure 6
IL-1α released by alveolar macrophages upon particle exposure mediates neutrophilic inflammation directly and via IL-1β production. In homeostasis, IL-1α is constitutively expressed by resident alveolar macrophages and intracellularly retained as preexisting stocks. Released IL-1α into the extracellular milieu by necrotic macrophages serves as alarmin after silica exposure. IL-1α is a potent activating stimulus required for surrounding macrophages to express the biologically inactive precursor IL-1β (pro-IL-1β). This form is cleaved by silica-induced inflammasome assembly and activation prior its secretion as mature and bioactive IL-1β. IL-1α and β relayed by their receptor (IL-1R) are necessary to generate pulmonary neutrophil accumulation in response to silica particles.