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Myofibroblasts: smooth muscle cell-fibroblast

  • Communicate by gap junctions
  • Provide wound contraction
  • Contract from center of wound?
  • Responsible for healing by secondary intention.

Collagen:

  • 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):

  1. Platelets
  1. PMN's
  1. Macrophages
  1. Fibroblasts (dominant by day 5)
  1. Lymphocytes

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.

GmCSF:

  • 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
  • Increase:
  • Fibrinogen
  • Amyloid
  • C-reactive protein (CRP, an opsonin)
  • Cerulopasmin
  • Haptoglobin
  • Alpha-1 antitrypsin
  • Decrease:
  • Fibronectin
  • Albumin
  • Transferrin

CXC chemokines: (C stands for Cysteine)

  • Chemotactic, important in angiogenesis, wound healing

Pages in category "Wound Healing/Cytokines"

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