Mast cells in wound healing

One of the most well described non-allergic functions of the mast cell is wound healing. Mast cells are involved in many functions integral to remodeling and closing wounds.

Immediately following formation of a wound, signals are sent to constrict vessels near the injury to decrease the risk of bleeding and infection. After bleeding has been minimized, the blood vessels become a little more permeable to let cells and molecules from the bloodstream into the injured area in order to promote healing and prevent infection. These actions activate the complement clotting system, which produces molecules C3a and C5a. These molecules bind to mast cells and induce degranulation.

Following degranulation, vessels become more permeable through the action of histamine and other mediators. Fibrinogen, important in clot formation, leaves the blood stream and accumulates in the tissue. This triggers thrombin to change fibrinogen to fibrin, forming a clot. Mast cells are active in preventing excessive clotting. Tryptase and heparin are released from granules bound together, and this complex degrades fibrogen and inactivates thrombin.

The extracellular matrix is the structures which give substance to groups of cells and vessels. Following wound formation, fibronectin and type III collagen molecules gather near the injury. Mast cell proteases chymase and tryptase break down the extracellular matrix molecules to make room for newly made cells to close the wound. It is also possible that mast cell mediator CMA1 breaks down fibronectin.

Granulation tissue forms when wounds are healing. Granulation involves several activities, such as cell proliferation, develop of blood vessels, and building of new skin. Fibroblasts, which make collagen and extracellular matrix molecules, are drawn to the injury by mast cell signaling. Once there, they are induced to proliferate by action of the presence of histamine, tryptase, heparin and fibroblast growth factor. Mast cell degranulation also drives generation of new blood vessels through action of histamine, heparin, chymase, fibroblast growth factor, VEGF and tumor necrosis factor. Formation and proliferation of new epithelial tissue is also encouraged by TGF-b1, histamine, IL-1a, IL-1b, IL-6, tryptase, and heparin.

Once enough new cells have been made, the fibroblasts become myofibroblasts to make new muscle. Histamine and tryptase mediate this step. The fibroblasts directly interact with mast cells. Mast cell proteases tryptase and chymase trigger the activation of several molecules that mediate remodeling of the extracellular matrix. The wound is closed following this remodeling and laying down of new skin.

References:

Douaiher, Jeffrey, et al. Development of Mast Cells and Importance of Their Tryptase and Chymase Serine Proteases in Inflammation and Wound Healing Advances in Immunology, Volume 122 (2014): Chapter 6.

Christine Möller Westerberg, Erik Ullerås, Gunnar Nilsson. Differentiation of mast cell subpopulations from mouse embryonic stem cells. Journal of Immunological Methods 382 (2012) 160–166.

 

 

 

4 Responses

  1. Pam June 17, 2015 / 6:46 am

    So interesting. I hope a follow up will deal with the healing process with too much tryptase and histamine. I will be reading this one again to see if I missed anything, which no doubt I have. Thanks, Lisa.

  2. Karen Neill June 17, 2015 / 6:09 pm

    Thanks Lisa.
    I have a question. How does somebody having MCAS affect wound healing? I’ve noticed that wounds take a ridiculous amount of time to heal with me (perfect example, I had a punch biopsy on my forearm 6 weeks ago, and it’s healing….very, very slowly. Most people may still have a slight red mark at this stage, but mine is still actively healing). I also tend to end up with almost no scar at all, and several of my scars have actually disappeared since I got very sick in 2011. I would think at having over active mast cells would aid in healing- but obviously not. Can you explain this paradox for me? There’s a distinct possibility that I have EDS as well, so is that what is causing the poor wound healing?

    Thanks,
    Karen

    • Lisa Klimas June 17, 2015 / 11:27 pm

      EDS is heavily implicated in poor wound healing. It is one of the ways people find out they have EDS – their skin won’t hold stitches and simple wounds keep splitting open. Overactivity of mast cells has shown incorrect remodeling of wounds such that they form heavy scars and fibrosis. It depends on a lot of factors, like what medications you take, as lots of medications also impact wound healing.

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