Wound Healing Stages

Stage

Hemostasis Inflammation

Proliferation

Remodeling

Cellular Components

Endothelial cells, platelets Neutrophils, macrophages, lymphocytes Endothelial cells, fibroblasts, cytokines, epithelial cells Fibroblasts, epithelial cells

Cellular Mediators and Activity

Fibronectin, platelet-derived growth factor Cytokines, interleukins, proteases

Collagen synthesis

Collagenases, gelatinases, degradation, metalloproteinases, stromelysins factors to clean up the wounded area. If this inflammation with associated reactive oxygen species (ROS) and catabolic enzymes is not halted, healing will not occur.

Once inflammation is controlled, new extracellular matrix is then formed with fibroblasts that begin the so-called proliferative phase. Fibrotic lesions (often in association with increased densities of mast cells) are characterized by excessive matrix deposition and reduced remodeling.

The cellular components and associated mediators of these stages can be found in Table 10.1.

Interleukins (about 20 have been identified) are cytokines produced by lymphocytes, monocytes, and macrophages. They regulate the cell-mediated response of the immune system. For example, interleukin-1 (IL-1) is involved in the triggering of the immune response, starting acute inflammation and maintaining chronic inflammation. Interleukin-2 (IL-2) is produced by helper T cells and induces proliferation of immune cells, both T and B. Interleukin-3 (IL-3) promotes the differentiation and proliferation of stem cells of the leukocyte family. Interleukin-6 (IL-6) is produced by various cells, including tumor cells, and acts as a stimulant of plasma proteins and B and T cells. Interleukin-12 (IL-12), produced by a range of cells, activates T cells and natural killer cells and promotes the response to a range of pathogens, including the human immunodeficiency viruses (HIV) of IL-2. It appears to be one of the most promising interleukins for the control of viral, bacterial, and protozoal infections.

Zinc, for example, is a trace element that is essential for immune functions. It directly induces monokine secretion by monocytes. There is also a specific inhibition of IL-1 receptor-associated protein kinase (IRAK) by zinc ions. Therefore, in contrast to an indirect stimulation of T cells due to zinc-induced monokines, higher concentrations of zinc directly inhibit T cell functions by means of specific inhibition of IRAK and subsequent signaling events, such as NFkB activation. The complex natures of these tiny nutrients are further illustrated by these divergent effects of zinc on different cell populations that depend on zinc concentration.34

Interferons are also cytokines belonging to a family of antiviral proteins that occur naturally in the body. a-Interferon and P-interferon probably exert an overall suppressive effect on the immune system. y-Interferon is produced by immune system cells and enhances T cell recognition of antigens.

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