Figure 1.

Anti-inflammatory strategies of alveolar macrophages favoring tissue damage control. Removal of apoptotic cells by Aφs (efferocytosis) leads to the secretion of anti-inflammatory mediators, such as transforming growth factor β1 (TGF-β1), prostaglandin E₂ (PGE₂), and platelet-activating factor (PAF), which in turn suppress the synthesis of pro-inflammatory cytokines, chemokines, and leukotriene C₄. During phagocytosis of apoptotic cells or in response to inflammation-associated cytokines, Aφs also release insulin-like growth factor 1 (IGF-1). Binding of IGF-1 to its receptor on epithelial cells changes their phagocytosis pattern. Epithelial cells reduce the clearance of apoptotic cells while increasing the uptake of anti-inflammatory macrophage-derived microvesicles containing suppressor of cytokine signaling proteins (SOCS). Contact-dependent intercellular communication between Aφs and epithelial cells, using connexin 43 (Cx43)-containing gap junction channels, leads to synchronized calcium waves, using the epithelium as the conducting pathway and drives anti-inflammatory actions. Finally, Aφs promote the differentiation of regulatory T cells to further control inflammation.