Guest guest Posted February 1, 2002 Report Share Posted February 1, 2002 : Here's what I have from my saved messages file. This article was originally sent by Myra. Barb London, Ontario, Canada May the wind be always at your back.mtnbiker@... mountainbiker41@... Prostagladin D2 Hi Guys, I recently wrote this answer to someone asking about celebrex verses NSAIDs for Prostagladin D2 control. In this piece I explain a little more about my understanding of the mast cell cascade. For those of you who haven't received a copy of my "Newbie Notes", let me know and I will send it to you. 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 " 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 " 2 Bank". But these guards, being very strict guards, will not let "Arachidonic Acid" enter the " 1 Bank either". And in the " 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 " 2 Bank" and leave the " 1 Bank" accessable to "Arachidonic Acid". This stops prostagladin from being formed. Which is great for arthritis patients. However, here is the kicker, 1 is has been found to be responsible for the early burst of PGD2 associated with mast cell activation, whereas 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 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 ============================================================ J Invest Dermatol 1995 Oct;105(4):532-5Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels inskin and increases the threshold to provocation of polymorphic lighteruption. LE, Durham BH, Fraser WD, Friedmann PSDepartment of Medicine, University of Liverpool, United Kingdom.The sunburn response is markedly reduced by dietary fish oil rich in omega-3polyunsaturated fatty acids. Because prostaglandins mediate thevasodilatation, we examined the effect of fish oil on ultraviolet (UV)B-induced prostaglandin metabolism. In addition we assessed the potentialphotoprotective effect of fish oil in light-sensitive patients. Thirteenpatients with polymorphic light eruption received dietary supplements offish oil rich in omega-3 polyunsaturated fatty acids for 3 months. Atbaseline and 3 months, the minimal erythema dose of UVB irradiation wasdetermined, and a graded UVA challenge given to a forearm to assess thethreshold dose for papule provocation. Suction blisters were raised on theother forearm, on control skin, and on skin irradiated with four times theminimal erythema dose of UVB 24 h previously, and blister fluidprostaglandin E2 was measured by radioimmunoassay. Following 3 months offish oil, the mean minimal erythema dose of UVB irradiation increased from19.8 +/- 2.6 to 33.8 +/- 3.7 mJ/cm2 (mean +/- SEM), p < 0.01. The UVAprovocation test was positive in 10 patients at baseline, and after 3 monthsnine 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 to27.2 (11) ng/ml after UVB, p < 0.01. Following 3 months of fish oil, PGE2decreased 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 maybe due, at least partially, to lowered prostaglandin E2 levels. Thephotoprotection against UVA-provocation of a papular response suggests aclinical application for fish oil in polymorphic light eruption.Publication Types:Clinical trialPMID: 7561154, UI: 96007598 ============================================================== 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 KDepartment 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 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~If you do wish to unsubscribe then you can click on the following link: <mailto:urticaria-unsubscribe (AT) e>~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~This list is in the service of those who suffer from Chronic Urticaria (hives). We strive to support and lift each other as a worldwide cyber-family. We share whatever needs to be shared to help one another in our struggle with Chronic Urticria. Any posting that is off the main topic of Chronic Urticaria, we post with a prefix of NCU -. This is done out of respect for those who do not wish to read such postings. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted February 1, 2002 Report Share Posted February 1, 2002 May the wind be always at your back. mtnbiker@... mountainbiker41@... Re: Prostagladin D2 > Urticaria > > Myra & wrote: > > > > Urticaria > > > > Hi Guys, > > > > I recently wrote this answer to someone asking about celebrex verses > > NSAIDs for Prostagladin D2 control. In this piece I explain a little > > more about my understanding of the mast cell cascade. For those of > > you who haven't received a copy of my " Newbie Notes " , let me know and > > I will send it to you. > > > > 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 " 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 " 2 Bank " . > > But these guards, being very strict guards, will not let " Arachidonic > > Acid " enter the " 1 Bank either " . And in the " 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 " 2 Bank " and > > leave the " 1 Bank " accessable to " Arachidonic Acid " . This stops > > prostagladin from being formed. Which is great for arthritis > > patients. However, here is the kicker, 1 is has been found to be > > responsible for the early burst of PGD2 associated with mast cell > > activation, whereas 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 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 > > ============================================================ > > 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. > > > > 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 > > ============================================================== > > 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 > > > > ---------------------------------------------------------------------- > > To unsubscribe, write to urticaria-unsubscribe@... > > Start Your Own FREE Email List at http://www.listbot.com/links/joinlb > > Do you think hivers should avoid foods which produce arachidonic acid? > I believe red meat and egg yolks are two of them. > > > ______________________________________________________________________ > To unsubscribe, write to urticaria-unsubscribe@... > > Start Your Own FREE Email List at http://www.listbot.com/links/joinlb > Quote Link to comment Share on other sites More sharing options...
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