Table 1. Hematopoietic cells, their functions and mediators released in tissue repair. This table also summarizes genetic mouse models of inflammation and cutaneous wound healing.
CXCL-4=CXC chemokine ligand 4; ECM=extracellular matrix; EGF=epidermal growth factor; MMP=matrix metalloproteinase; NETs=neutrophil extracellular traps; PDGF=platelet derived growth factor; PF4=platelet factor 4; Pg=plasminogen; TGF-β= transforming growth factor-β, uPA= urokinase plasminogen activator, uPAR= urokinase plasminogen activator receptor.
| Phase | Coagulation factor/Blood component | Growth factor, Mediator | Effect | Mechanistic insight from murine knockouts (reference) |
|---|---|---|---|---|
| Hemostasis | Platelets | PDGF | Chemotaxis of macrophages, fibroblast mitogen | |
| EGF | Keratinocyte proliferation | |||
| CXCL-4 PF4 | Recruitment of inflammatory cells | |||
| Factor IX | Early and late wound healing (cutaneous and joint), macrophage inflammation | Hemophilia B mice: Delayed dermal wound healing with bleeding into granulation tissue (63); delayed macrophage infiltration (64); defective joint healing (65) | ||
| Factor XIII | Re-epithelialization and wound closure | FXIII deficient mice: Delayed re-epithelialization compared to controls (67) | ||
| Inflammation | Neutrophils | Serine proteases; NETs | Antimicrobial activity | Cathepsin G deficient mice: increased neutrophilic inflammation, delayed wound healing (76) |
| MMPs | ECM degradation, cell migration | PU.1 null mouse: normal wound healing as wild type mice (77) | ||
| Macrophages | Inflammation, angiogenesis M1: host defense M2: wound repair | Prevention of macrophage infiltration: defective wound healing (78) | ||
| Transgenic mice with macrophage elimination: Impaired re-epithelialization, collagen deposition and angiogenesis (79) | ||||
| Protease expression, re-epithelialization and angiogenesis | Plasminogen | Extracellular proteolysis | Pg deficient mice: Delayed wound healing and prolonged inflammation (69, 70) | |
| uPA | Extracellular proteolysis (via Pg activation) | uPA knockout mice: Impaired wound healing (73) | ||
| uPAR | Extracellular proteolysis, inflammation (via FXII) | uPAR knockout (Plaur−/−)mice: no defects in wound healing (73) | ||
| Plau(GFDhu/GFDhu) mice: selective abrogation of uPA-uPAR interaction: no disruption of wound healing (74) | ||||
| Tissue remodeling | Platelets | TGF-β | Wound contraction | CD18 deficient mice: defective wound contraction (80) |
| Macrophages Macrophages | Wound contraction | |||