Here's the deal......... when mast cells or basophils degranulate they trigger many things to happen.  Here is one of the things that happens which causes swelling and angioedema. 

 

Mast cells contain a chemical called arachidonic acid, which is stored lipids (liquid fats)  within the cell.   (Arachidonic Acid can also be found in macrophages, monocytes, eosinophils and basophils.)  When mast cells degranulate they start a very complicated chain of events.   One thing that happens is that arachonic acid is released from cell membrane phospholipids by the activation of phospholipase A2.  After it's release, arachidonic acid undergoes a change (metabolizes)  through  two pathways. The first and most common pathway is the cyclooxygenase pathway, producing prostaglandins and thromboxanes, and the second pathway is the 5-lipoxygenase pathway, producing leukotrienes, (LTC4).   It is believed that skin mast cells tend to produce far more PGD2 and  intestinal mast cells tend to produce far more leukotrine C4.  Just for reference, 
prostaglandins D2 (PGD2) constrict smooth muscles (particularly in the lungs), attract neutrophils (a type of white blood cell) and inhibits the aggregation of platelets, which is the first step to blood clotting. (PAF)   It helps the blood vessels to dialate and become "leaky".   Leukotrienes also cause the  constriction of the smooth muscle fibers in the lungs and blood vessels, and increased secretion of mucus.  Leukotrienes attract eosinophiles, another type of white blood cells.

 

It should be remembered that mast cells produce many more things through this cascade, including various types of proinflammatory and growth factor cytokines, including tumor necrosisfactor (TNF), interleukin-3 (IL-3), IL-4, and IL-16.

 

Think of a revolving door in one of those old bank buildings.   The bank is named  "Cox 2"  (one of two kinds of cyclo-oxygenases).  A man called "Arachidonic Acid" walks in the door picks up two briefcases (two oxygen molecules) and walks back out................. he entered the bank not being a bad guy but exited with "baggage" and is now a criminal  (prostagladin).  NSAIDs and Aspirin act like the national guard which will not let "Arachidonic Acid" enter the "Cox 2 Bank".    But these guards, being very strict guards,  will not let "Arachidonic Acid"  enter the "Cox 1 Bank either".  And in the "Cox 1 Bank" Anachidonic Acid is needed to produce good prostagladin.  Good prostagladins help to maintain the lining of the stomach and intestine, as well as aid in kidney function and blood clotting. 

 

Celebex was designed by Searle to guard only the "Cox 2 Bank" and leave the "Cox 1 Bank" accessable to "Arachidonic Acid".   This stops prostagladin from being formed.  Which is great for arthritis patients.   However, here is the kicker, Cox 1 is has been found to be responsible for the early burst of PGD2 associated with mast cell activation, whereas Cox 2 is associated with the prolonged generation of the prostanoid, which occurs later in the allergic reaction.  Which means that people who are mast cell degranulators need the "national  guard" not just the Cox 2 bank guard.  

 

There is a book called "Mast Cell in Health and Disease" that many of the masto people have read.  In it it explains how Omega 3 Fish oil works.  Evidently the fat from Omega 3 is stored in cells which store Arachidonic Acid, such as mast cells.  When the mast cell degranulates and tries to make PGD2, it can't, because Omega 3 is the wrong lipid.  Kind of like not having the right ingredients for a recipe you are trying to create.   Can you imagine trying to use olive oil instead of vegetable oil in a delicate cake recipe.   Same idea........it won't work.    Hope this helps.  Hugs, Myra

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J Invest Dermatol 1995 Oct;105(4):532-5


Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels in
skin and increases the threshold to provocation of polymorphic light
eruption.

Rhodes LE, Durham BH, Fraser WD, Friedmann PS

Department of Medicine, University of Liverpool, United Kingdom.

The sunburn response is markedly reduced by dietary fish oil rich in omega-3
polyunsaturated fatty acids. Because prostaglandins mediate the
vasodilatation, we examined the effect of fish oil on ultraviolet (UV)
B-induced prostaglandin metabolism. In addition we assessed the potential
photoprotective effect of fish oil in light-sensitive patients. Thirteen
patients with polymorphic light eruption received dietary supplements of
fish oil rich in omega-3 polyunsaturated fatty acids for 3 months. At
baseline and 3 months, the minimal erythema dose of UVB irradiation was
determined, and a graded UVA challenge given to a forearm to assess the
threshold dose for papule provocation. Suction blisters were raised on the
other forearm, on control skin, and on skin irradiated with four times the
minimal erythema dose of UVB 24 h previously, and blister fluid
prostaglandin E2 was measured by radioimmunoassay. Following 3 months of
fish oil, the mean minimal erythema dose of UVB irradiation increased from
19.8 +/- 2.6 to 33.8 +/- 3.7 mJ/cm2 (mean +/- SEM), p < 0.01. The UVA
provocation test was positive in 10 patients at baseline, and after 3 months
nine of these showed reduced sensitivity to papule provocation, p < 0.001.
Before fish oil, PGE2 increased from 8.6 (SEM 2.1) ng/ml in control skin to
27.2 (11) ng/ml after UVB, p < 0.01. Following 3 months of fish oil, PGE2
decreased to 4.1 (1) and 9.6 (2.4) ng/ml in control and irradiated skin,
respectively, p < 0.05. Reduction of UV-induced inflammation by fish oil may
be due, at least partially, to lowered prostaglandin E2 levels. The
photoprotection against UVA-provocation of a papular response suggests a
clinical application for fish oil in polymorphic light eruption.

Publication Types:
Clinical trial

PMID: 7561154, UI: 96007598

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Eicosapentaenoic acid inhibits prostaglandin D2 generation by inhibiting cyclo-oxygenase-2 in cultured human mast cells.

Obata T, Nagakura T, Masaki T, Maekawa K, Yamashita K

Department of Molecular Cell Biology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan.

BACKGROUND: Eicosapentaenoic acid (EPA) is catalysed by cyclo-oxygenase (COX), as is arachidonic acid, and is a competitive inhibitor of arachidonate metabolism. OBJECTIVES: We examined the effect of EPA on prostaglandin (PG) D2 generation in the cultured human mast cells with IgE-anti-IgE challenge incubation. METHODS: Cultured human mast cells were incubated with EPA (1 micromol/L) for 20 h, then challenged with anti-IgE incubation after treatment with IgE. At the same time, COX inhibitors were tested to identify COX-1 and COX-2 activity. PGD2 synthetic activity was also assayed in a cell-free homogenate of cultured mast cells with COX inhibitors and EPA. Histamine in the culture medium and in cells was assayed with the HPLC-fluorescent method. PGD2 and PGD3 were assayed with gas chromatography-mass spectrometry and the stable isotope dilution method. RESULTS: Although EPA incubation did not affect histamine release by cultured human mast cells in response to IgE-anti-IgE challenge incubation, it did decrease PGD2 generation by inhibiting the COX-2 pathway. In contrast, in the cell-free homogenate of cultured human mast cells, EPA inhibited both COX-1 and COX-2 activities. CONCLUSION: Pre-incubation with EPA primarily affects the COX-2 pathway in cultured human mast cells and reduces PGD2 generation in response to IgE-anti-IgE challenge incubation. These findings suggest that COX-1 and COX-2 have different substrate flow systems in mast cells. They also suggest that endogenous EPA diet supplementation would reduce PGD2 production and could serve as an anti-inflammatory substrate in human mast cells.

PMID: 10457118, UI: 99388311