Myofibroblasts: smooth muscle cell-fibroblast
- Communicate by gap junctions
- Provide wound contraction
- Contract from center of wound?
- Responsible for healing by secondary intention.
- Is glycine x3. alpha-ketoglutarate, vit C, O2, Zn and iron all needed for prolyl hydroxylase, crosslinking
- Collagen production begins day 3, max at day 21 then constant amount but more crosslinking, strength
- Collagen Type I: most abundant throughout
- Principal collagen in scar (late)
- Collagen Type II and XI: in cartilage
- Collagen Type III: in healing wound. Low in Ehler-Danlos type IV
- C. Type III becomes C. type I with maturation ~ @ week 3
- Collagen Type IV: in basement membranes
Tensile strength: never equal to pre-wound
- At 6 weeks: wound is 60% of its original strength
- At 8 weeks: wound reaches maximum tensile strength, which is 80% of its original tensile strength.
Opening a 5-day or older wound: results in quicker healing the 2nd time (cells, products already in place)
Administering vitamin A: reduces deleterious effects of steroids on wound healing
Cells to wound (in order):
- Fibroblasts (dominant by day 5)
Macrophages are essential.
TGF-ß: stimulates fibroblasts
- Chemotactic for neutrophils. Speeds healing
- Too much/too long -> fibrosis (e.g. cirrhosis, pulmonary fibrosis)
PDGF: (active agent in Regranex)
- Attracts fibroblasts and increase smooth muscle to speed matrix deposition and collagen formation.
- Used in chemotherapy patients to increase neutrophil and macrophage activity.
TxA2: (from platelets) platelet aggregation, vasoconstriction.
PGI2: (prostacyclin): platelet inhibition, vasodilation and bronchodilation
Initial cytokine response to injury/infection: dependent on TNF/IL1 (synergistic), CXC, and IL6
TNF: main source is Macrophage/Monocyte.
- Endotoxin (LPS a) is most potent stimulus for production.
- Overall has pro-coagulant effect
- Responsible for wasting, cachexia in cancer patients, by lipolysis, glycolysis, anorexia
- Recruits, activates neutrophils è more cytokines, free radicals.
- Exaggerated response è MOSF
IL-1: (also from macrophages)
- Potentiates TNF
- Responsible for fever
- Acts to increase IL-6 (acute phase response)
- Increase endothelium adherence via selectins, ICAM, VCAM
Acute phase response:
- Increase fever, catabolism
- C-reactive protein (CRP, an opsonin)
- Alpha-1 antitrypsin
CXC chemokines: (C stands for Cysteine)
- Chemotactic, important in angiogenesis, wound healing