The Inflammatory Phase

The inflammatory phase is characterized by initiation of the clotting cascade, increased vascular permeability by the release of cytokines and other chemical mediators, and chemotaxis of cells and their subsequent activation. The initial event after injury is the activation of the coagulation cascade that results from the exposure of platelets to exposed subendothelial collagen from injured vessels (8). This recruitment and aggregation of platelets not only result in formation of a clot but also trigger the release of various cytokines and growth factors through the process of platelet degranulation (9). These mediators include platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-p), platelet-activating factor (PAF), fibronectin, serotonin, prostaglandins, thromboxanes, leukotreines, and proteases. The release of these substances into the wound milieu is chemotactic for neutrophils, macrophages, lymphocytes, fibroblasts, and endothelial cells. These cells are then activated and release their own specific mediators (Fig. 1).

Fibronectin forms cross-links within the clot and provides a scaffold for migrating keratinocytes, endothelial cells, and fibroblasts (10,11). It has been demonstrated experimentally in animals that in the absence of fibrinogen, clot formation fails and wound repair is significantly hindered.

Neutrophils are the first inflammatory cells to arrive at the injured site (Fig. 2). They gain access to the wound via increased vascular permeability and are recruited and activated by a concentration gradient of chemotactic substances such as

Figure 1 The phases of soft tissue wound repair and cellular and mediator interaction. (From Wong ME, Hollinger JO, Pinero GJ. Integrated processes responsible for soft tissue healing. Oral Surg Oral Med Oral Pathol 1996;82:475-92.)

Maturation Pro literal ion

Inflammation

Maturation Pro literal ion

Inflammation

Days Posiwoun cling

Figure 2 The chronology of cellular migration into the wound. (From Ref. 7.)

Days Posiwoun cling

Figure 2 The chronology of cellular migration into the wound. (From Ref. 7.)

prostaglandins, complement factors, interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, TGF-p, and bacterial products. The number of neutrophils in the wound is at its greatest concentration 2 days after the initial injury. Cell surface receptors also play an important role in neutrophil migration. Specific receptors found on the endothelial cells (selectins) and on the neutrophil cell surface (integrins) assist in adherence to the endothelium and the extracellular matrix, respectively. The primary role of neutrophils is to provide an antibacterial defense.

Macrophages are involved in the second wave of inflammatory cell migration. Studies have shown that macrophages are the most important cellular component in the process of wound healing (12). It is well documented that normal wound healing can occur in the presence of neutropenia but cannot occur in the absence of macrophages. Chemotactic agents released during platelet degranulation recruit macrophages to the wound.

Upon arrival at the site of injury, macrophages are activated by cytokines and growth factors released by platelets. This activation signals the release of specific cytokines and growth factors by macrophages that are important in mediating four major processes (Fig. 3). These include (1) angiogenesis through the release of fibroblastic growth factor (FGF) (and vascular endothelial growth factor (VEGF); (2) regulation of matrix synthesis through the release of TGF, PDGF, TNF-a, interferon (IFN), IL-1, and prostaglandins; (3) phagocytosis/antimicrobial function and wound debridement through production of free radicals and enzymes; and (4) cellular recruitment and activation of fibroblasts. This multifactorial role of macrophages is instrumental in directing the future course of wound healing.

The recruitment and activation of lymphocytes occur late in the inflammatory phase (days 5-10). The function of lymphocytes is not completely clear but they may play a role in augmenting macrophage expression and fibroblast accumulation and proliferation through the release of IFN, IL-2 and macrophage-activat-ing factor. T lymphocytes appear to have some regulatory role in mediating macrophage function.

How To Reduce Acne Scarring

How To Reduce Acne Scarring

Acne is a name that is famous in its own right, but for all of the wrong reasons. Most teenagers know, and dread, the very word, as it so prevalently wrecks havoc on their faces throughout their adolescent years.

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