Prostaglandin E2, mast cells and asthma

In the mast cell community, we talk about prostaglandins a lot. Most of the time we are talking about prostaglandin D2, as it is well produced by mast cells. However, there are a number of other prostaglandins that can affect inflammation and disease processes.

Prostaglandin E2 has been inflammatory and anti-inflammatory effects in the body. It is the prostaglandin responsible for inducing fevers. It is also a vasodilator, which contributes in some models to swelling. It relaxes smooth muscle and interferes with release of norepinephrine. PGE2 can cause hyperalgesia, or exaggerated pain response, a hallmark of inflammation. It regulates blood pressure, body temperature, sleep-wake pattern, kidney function and peristalsis (movement through the GI tract), and intestinal secretion.

It activates T cells and favors development of certain types of T cells that participate in the allergic response. It also modulates B cell activity and allergic reactions. However, it makes other immune cells less active. PGE2 simulates bone resorption and is important in reproduction, softening the cervix and causing uterine contractions.

PGE2 has a number of interactions with mast cells. In mast cells from bone marrow or peritoneal cavity, it induces histamine, IL-6 and GM-CSF release. However, in mast cells from progenitor cells or in the lung, it decreases release of leukotrienes, TNF and histamine. PGE2 acts on mast cells to reduce expression of PGE receptors, EP2 and EP3. PGE2 can enhance IgE production by B cells but also interferes directly with mast cell degranulation stimulated by IgE.

Prostaglandin E2 has a very unusual relationship with allergic inflammation. In contrast to prostaglandin D2, which constricts the airway, PGE2 actually relaxes the smooth muscle and opens the airway. Importantly, PGE2 retains this ability regardless of the trigger for reactive airway – allergen, asthma or exercise. Curiously, it was observed early on to cause coughing.

An interesting fact is that administration of medications that interfere with COX-2 (like Celebrex or aspirin) can worsen airway function and increase inflammation. This is of particular note in asthma patients. It is thought that this may be due to reducing production of PGE2.

 

References:

Emanuela Ricciotti, Garret A. FitzGerald. Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol. 2011; 31: 986-1000.

Rosa Torres, César Picado, Fernando de Mora. The PGE2–EP2–mast cell axis: An antiasthma mechanism. Molecular Immunology 63 (2015) 61–68

Daniel F. Legler, Markus Bruckner, Edith Uetz-von Allmen, Petra Krause. Prostaglandin E2 at new glance: Novel insights in functional diversity offer therapeutic chances. The International Journal of Biochemistry & Cell Biology 42 (2010) 198–201.

2 Responses

  1. Juceila May 7, 2015 / 8:43 pm

    In acquired dirosders of granulopoiesis it is not uncommon to see eosinophils in which some granules have basophilic staining characteristics. These are immature granules, sometimes termed Pro-eosinophilic granules*. Such cells are increased in frequency in CGL, eosinophilic leukaemia and certain categories af AML, in which eosinophils are part of the leukaemic clone, particularly cases of AMML with eosinophilia associated with inversion of chromosome 16. . But recent evidence has shown, that in some patients with CLG there are also hybrid cells with a mixture of granules of eosinophil type and baosphil type. Nice photo thank You very much.

  2. NATALIE May 25, 2016 / 4:08 pm

    You are incredible.
    I had a test for PGD2 and apparently the lab accidentally did pgE2. Besides the lab technicians not noticing when they compared it to the order (which I double checked), I printed out the results…I thought it didn’t seem right but was new to the mast cell world.
    THREE DIFFERENT DOCTORS (2 of which specialize mast cell activation disorders) looked at the print out which CLEARLY says pgE2 and said, well that’s very high….it appears you have mast cell activation disorder! I was sooooo excited I finally got a diagnosis after a full year of searching for just a mast cell doctor.
    9 months later, one of the drs realized that the test was for pgE2 and not D2. She only realized after I asked her to write a letter on my behalf stating the results and what the disorders is, etc. Suddenly, she jumps off my case until I get pgD2 results.
    And that was it. I then asked no joke 8 different doctors of all different specialists and no one would tell me what pgE2 meant. And doesn’t anyone care or think it might help to know what it means since my levels were twice as high as they should be? Multiple doctors said there was nothing out there on prostaglandin E2.
    Reading this just blows me away. Not to mention it makes complete sense to my case. Truly incredible. Thank you.

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