Lesser known mast cell mediators (Part 1)

I have posted at length about the roles of histamine and serotonin. Here are some less well known mast cell mediators. I will be doing in depth posts on the more relevant substances in the near future.

Monocyte chemotactic protein 1 (MCP-1), also known as chemokine ligand 2 (CCL2), draws other white blood cells, including memory T cells, monocytes and dendritic cells, to the site of injury or infection. It has important functions in neuroinflammation as seen in experimental autoimmune encephalitis, traumatic brain injuries, epilepsy and Alzheimer’s disease; and in diseases with pathologic infiltration of monocytes, like rheumatoid arthritis.

Chemokine ligand 3 (CCP7) recruits monocytes and regulates macrophage activity. It is known to interact with MMP2.

MMP2 (matrix metalloproteinase 2) is involved in tissue remodeling, reproduction and fetal development. It degrades type IV collagen. It has regulatory effects on the menstrual cycle and has been tied to growth of new blood vessels.

Interleukin 8 (IL-8), also known as neutrophil chemotactic factor (NCF), draws other white cells, mostly neutrophils, to a site of infection. It can activate multiple cells types, including mast cells, and promotes degranulation. It has been linked to bronchiolitis, psoriasis and inflammation.

MCP-4 (CCL13) attracts T lymphocytes, eosinophils, monocytes and basophils to an area of inflammation. Improper regulation can exacerbate asthma symptoms. Mast cells can release MCP-1 when stimulated by TNF-a and IL-1.

CCL5 (RANTES) attracts T cells, eosinophils and basophils. When IL-2 and interferon-γ are present, CCL5 activates natural killer cells and causes proliferation of the same. It is also important in bone metabolism.

CCL11 (eotaxin-1) specifically recruits eosinophils and is heavily involved in allergic inflammatory responses.

CPA3 (carboxypeptidase A3) digests proteins. It is released complexed with heparin proteoglycan along with chymase and tryptase.

Both interferon α (IFN- α) and interferon β (IFN-β) are made in response to viral infections. Their activities are regulated by IFN- γ. IFN- γ also draws white cells to the site of inflammation. Failure to properly regulate interferon levels can cause autoimmune disease. Interferons are so called because of their ability to “interfere” with viral infection. They are responsible for “flu type symptoms,” such as fever, muscle aches and lethargy.

All mediators listed here are produced by mast cells and stored in granules until degranulation.


2 Responses

  1. Mary November 18, 2014 / 7:11 am

    Hai, I am from a country where food allergies are almost unheard here. We dont have any family history of allergies. During my pregnancy I took Alfacalcidol 0.25mcg per day from propably fifth month of gestation. My kid who is three years now has severe non Ig E mediated food allergies resulting in green mucusy diarrhoea to bloody stool during reactions. I have a strong feeling that its all because of the Alfacalcidol I took during my pregnancy. Is there a possibity that any of these mediators are release more because of Alfacalcidol intake? TIA

    • Lisa Klimas November 18, 2014 / 2:53 pm

      I am sorry to hear that your son is having such a hard time. In mast cell patients, essentially any substance can cause a reaction. However, that does not mean it caused your son to have these health issues. We are still learning why some people develop mast cell disease (or other severe allergic diseases, like FPIES), but it seems to be the case that there is a genetic predisposition that is “activated” at some point in life. Many researchers believe that these genetically predisposed people will eventually be activated by something. I do not have any reason to believe that the alfacalcidol contributed to your son’s allergies. I know a lot of mothers who feel that something they did while pregnant contributed to their children developing food allergies or mast cell issues. I have not found any evidence that that is the case. I wish you and your son all the best.

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