Allergic effector unit: The interactions between mast cells and eosinophils

Eosinophils are granulocytes that can localize to the tissues under certain conditions, including allergic response. Eosinophilic granules contain the positively charged proteins major basic protein, eosinophil peroxidase, eosinophil cationic protein, and eosinophil-derived neurotoxin. Like mast cells, eosinophils release these granules in response to many things, including inflammatory signals, parasitic infection, tissue damage and allergic inflammation. They express many receptors, including receptors for platelet activating factor (PAF) and histamine receptors. PAF and histamine are both released by mast cells.

Mast cells and eosinophils are overwhelmingly found together in late and chronic stages of allergic inflammation. They function in such close concert that mast cells, eosinophils and their effects have been termed the allergic effector unit (AEU). Mast cells release signals that affect eosinophil behavior and receive signals from eosinophils. These cells often also function while in physical contact with one another. When eosinophils are in physical contact with mast cells, they live longer than normal. CD48, 2B4, DNAM-1 and Nectin-2 are all involved in the mast cell – eosinophil contact mechanism.

Major basic protein can activate mast cells and eosinophil peroxidase is taken up by mast cells as a signaling molecule. Tryptase draws eosinophils to mast cells and causes release of eosinophil peroxidase, IL-6 and IL-18 from eosinophils. Histamine and prostaglandin D2 also signal eosinophils to migrate towards mast cells. Mast cell secreted eotaxin activates eosinophils by the histamine 4 (H4) receptor. Both cell types secrete leukotrienes and both express leukotriene receptors.

When grown together, researchers are able to investigate the behavior of mast cells and eosinophils together. This is called co-culture. In 29% of cases, eosinophils will migrate towards resting (non-activated) mast cells. In 45% of cases, eosinophils will migrate towards IgE activated mast cells. In 47% of cases, eosinophils will migrate towards mast cells activated through a non-IgE pathway. The specific attractant signal has not been identified.

When co-cultured with eosinophils, basal mast cell mediator release was 5% higher. When the mast cells were activated by IgE, degranulation was 15% higher. In order to activate mast cells, eosinophils must be in contact with them. However, mast cells can activate eosinophils without contact. In co-cultures with mast cells, eosinophil peroxidase constituted 47% of eosinophil released proteins, compared with 18% normally.

In low term co-cultures, both mast cells and eosinophils stayed activated. TNF was high in the co-culture, but not IL-6, IL-8 and IL-10. Importantly, low relative numbers of mast cells could activate eosinophils, but mast cell activation was most effective when eosinophils were more numerous. Eosinophils are thought to reduce the threshold of mast cell responsiveness to IgE.

 

References:

Elishmereni M, Bachelet I, Nissim Ben Efraim AH, Mankuta D, Levi-Schaffer F. Interacting mast cells and eosinophils acquire an enhanced activation state in vitro. Allergy 2013; 68: 171–179.

Elishmereni M, Alenius HT, Bradding P, Mizrahi S, Shikotra A, Minai-Fleminger Y, et al. Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro. Allergy 2011;66:376–385.

Minai-Fleminger Y, Elishmereni M, Vita F, Soranzo MR, Mankuta D, Zabucchi G et al. Ultrastructural evidence for human mast cell-eosinophil interactions in vitro. Cell Tissue Res 2010;341:405–415.

Puxeddu I, Ribatti D, Crivellato E, Levi- Schaffer F. Mast cells and eosinophils: a novel link between inflammation and angiogenesis in allergic diseases. J Allergy Clin Immunol 2005;116:531–536.

5 Responses

  1. Mark Beckwith April 7, 2015 / 9:59 am

    Umm…thanks Lisa…[layperson blather follows]…this is great stuff to know, but could you elaborate on why they would have taken an eosinophil count for my wife (diagnosis: idipoathic anaphylaxis)? What are allergists trying to find out when they count eosinophils in a case like this?

    • Lisa Klimas April 8, 2015 / 11:15 pm

      Eosinophils are inflammatory cells, so more eosinophils than expected is a marker of inflammation. Eosinophils can also cause their own GI disease, and it is important to distinguish whether a patient has mast cell activation from eosinophilic disease or eosinophilic activation from mast cell disease. Very tricky. But they differ in important ways – some treatment options are different, and patients with eosinophilic GI disease can sometimes achieve remission.

  2. MRuiz July 8, 2015 / 5:44 pm

    Hi. Lisa. I’m not the best in terms of scientific terminology. However, Does low or high platelet blood levels have anything to do with the “platelet activating factor”? During flare ups with my son (which are mostly triggered by foods) often has a low platelet level, but doctors are not sure why. He also has eosinophilic esophagitis. Thanks in advanced.

    • Lisa Klimas July 10, 2015 / 11:11 pm

      I’m not aware of a direct link between level of PAF and platelet count. Does he have a normal count the rest of the time?

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