Wound Healing, Cytokines

• Myofibroblasts (smooth muscle/fibroblast) provide wound contraction. Contract from center of wound. Responsible for healing by secondary intention
• Collagen Type I: most abundant throughout. Principal collagen in scar (late). Type III: in healing wound, low in Ehler Danlos. Type IV: in basement membrane.  Type XI (and II) in cartilage
• Collagen is glycine q3. alpha-ketaglutarate, vit c, O2, and iron needed for prolyl hydroxylase, crosslinking
• Collagen production begins day 3, max at day 21 then constant amount but more crosslinking, strength
• Type III becomes type I with maturation ~ 3 weeks
• Tensile strength never equal to pre-wound
• Opening a 5 day or older wound results in quicker healing the second time (cells, products already in place)
• Giving Vit A reduces deleterious effects of steroids on would healing
• Cells to wound (in order): platelets, pmn's, macrophages, fibroblasts (dominant by day 5). Macs essential
• TGFB stimulates fibroblasts; too much/too long -> fibrosis (i.e. cirrhosis, pulmonary fibrosis). Also chemotactic for neutrophils. Speeds healing.
• PDGF attracts fibroblasts and increases smooth muscle (active agent in Regranex) to speed matrix deposition and collagen formation
• GmCSF is used in chemotherapy patients to increase neutrophil and macrophage activity
• TxA2 from platelets; plt aggregation, vasoconstriction
• PGI2 (prostacyclin): plt inhibition, vasodilatation, and bronchodilation
• Initial cytokine response to injury/infection dependent on TNF/IL 1 (synergistic), CXC, IL 6
• TNF: main sourse 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 -> more cytokines, free radicals. Exaggerated response -> MOSF
• IL-1 also from macs/monos; potentiates TNF; responsible for fever. Acts to increase IL6 (acute phase response), increase endothelium adherence via selectins, ICAM, VCAM
• Acute phase response: increase fever, catabolism. Increase C-reactive protein (CRP, an opsonin), amyloid, fibrinogen, haptoglobin, ceruloplasmin, and alpha-1 antitrypsin. Decrease levels of albumin, transferin and fibronectin
• CXC chemokines: chemotactice, important in angiogenesis, wound healing. C stands for Cysteine

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