Figure 1.

Phases of tissue repair in the context of myeloid cells. (1) Clotting (top right) is the first step after injury takes place. Damage to alveolar epithelial cells (AEC) leads to the aggregation of erythrocytes and platelets that form a blood clot to contain spreading of the damage. The destruction of the tissue causes release of damage‐associated molecular patterns (DAMPs), or allows the entrance of microorganisms and thereby pathogen‐associated molecular patterns (PAMPs). Local cells such as dendritic cells, macrophages, and AECs are activated by DAMPs and PAMPs through toll‐like receptors (TLRs) and protease‐activated receptors (PARs) and produce the first round of pro‐inflammatory mediators. (2) Inflammation (bottom right) involves the infiltration of neutrophils and monocytes that respond to the pro‐inflammatory stimuli that were produced by resident lung cells. Phagocytes such as neutrophils and macrophages remove tissue debris and potentially threatening particles. In this pro‐inflammatory environment, monocytes and resident macrophages can differentiate into M1 macrophages that further promote inflammatory responses by the production of pro‐inflammatory mediators such as IL‐6 and TNF‐α. (3) Repair (bottom left) is the phase in which inflammatory responses subside and turn into repair responses through the effects of anti‐inflammatory and pro‐repair cytokines such as IL‐10 and TGF‐β. In this stage fibrocytes enter the tissue and differentiate into fibroblasts that proliferate and turn into the more contractile myofibroblasts. Myofibroblasts produce extracellular matrix (ECM) to close the open wound and form a scar. M2 macrophages predominate in this stage and produce mediators that contribute to the proliferation of fibroblasts and the deposition of ECM. (4) Resolution (top left) refers to the last phase in tissue repair in which excess ECM is degraded to make space for new cells. At the end of this stage the tissue has regained its structure and function