Inflammation

The inflammatory phase begins with an injury or insult that stimulates an inflammatory response by exposure of subendothelial collagen to platelets, which activates the intrinsic and extrinsic clotting cascades and causes platelet degranulation, with release of cytokines and growth factors from platelet a-granules. These platelet-produced growth factors like platelet-derived growth factor (PDGF) and transforming growth factors alpha (TGF-a) and beta (TGF-p) are released locally in the wound and amplify the recruitment of PMNs, and more importantly macrophages. After a brief vasoconstrictive phase mediated by thromboxane and serotonin that aids in hemostasis, a vasodilatory reaction (in response to platelet histamine release and prostaglandin generation) follows with migration of leukocytes, neutrophils (PMN), and later, macrophages into the wound along the fibrin clot scaffolding.

PMNs are the predominant cell type early on and migrate into the wound through an increase in vascular permeability and track along chemotactic gradients compromised of cytokines, complement cascade products (C3a and C5a), and growth factors in a process called margination. Endothelial receptors called selectins help PMNs loosely adhere to the involved area before integrin receptors on the PMN allow firm interaction and allow subsequent migration between endothelial cells into the extracellular matrix (ECM).

PMNs are an important adjunct, but not a necessity, for wound healing. They serve to promote bacterial clearance and debride the wound, but provide no essential growth factors.

Monocytes migrate into the wound and undergo transformation into activated macrophages at close to 48 hours, and their subsequent production of inflamatory cytokines (IL-1 and TNF) and growth factors (specifically transformation growth factor-p [TGF-p] and PDGF) appears to be the most critical cell-driven event of this entire phase. Their absence is associated with failure to progress to normal fibro-blast recruitment and function. This is in contrast to experiments which show wound healing to progress in the absence of PMNs and lymphocytes. Macrophages also serve a number of other important functions including nitric oxide synthesis, wound debridement, phagocytosis of bacteria, and stimulation of angiogenesis.

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