Smash and gag: Life with an avocado allergy




non ige mediated allergy :: Article Creator

The Future Of IgE-mediated Allergy Research And Treatments

In her laboratory, Cecilia Berin, Ph.D., the Bunning Professor of Food Allergy Research, studies the immune basis of allergy and tolerance to foods.

In a recent editorial published in the Journal of Experimental Medicine, Berin discusses the current state of treatments for IgE-mediated food allergies (which currently affect roughly 8% of the U.S. Population), targeting type 2 immune responses and next steps for food allergy research and treatment development.

What are IgE-mediated food allergies and how are they diagnosed?

The basis of IgE-mediated food allergies lies in a type of antibody called IgE. When these antibodies see the allergens for which they are specific—whether that's pollen, peanuts or something else—the allergens bind to the antibodies and those antibodies activate cells called mast cells or basophils. Those mast cells and basophils release chemicals like histamine that can cause allergic reactions.

Generally, what indicates an IgE-mediated food allergy is timing, that it occurs within minutes up to two hours after exposure. The symptoms are quite standard: hives, respiratory symptoms, nausea and vomiting. Physicians will administer a couple of different tests to check for IgE antibodies. One method is skin testing, where they put a small amount of the food allergen into the skin, and it causes a wheal and flare reaction if there are IgE antibodies present. There are also blood tests that can detect IgE antibodies specific to different foods.

What types of immune responses lead to IgE-mediated allergies?

B-cells can make different kinds of antibodies. They can make IgG antibodies or IgA antibodies that are protective against conditions such as bacterial infection. T-cells —specifically CD4+ T-cells—instruct the B-cell about what kind of antibody to make and CD4+ T-cells make type 2 cytokines that can instruct B-cells to make IgE antibodies. So, before someone has an allergic reaction, they have to already have been exposed to that food or antigen, and during that exposure, there is a generation of a type 2 cytokine response from a type of CD4+ T-cell called the T follicular helper cell that can instruct B-cells to make IgE.

What therapies are available for IgE-mediated food allergies and how effective are they?

There is currently only one FDA-approved treatment and that is for peanut allergy, and it is a treatment called Palforzia, and it's basically a peanut powder that is given in small doses and increases in amount over time as individuals become desensitized to that protein. So, the idea is that ingestion leads to desensitization of mast cells and basophils, it causes a change in the antibodies that are produced against that food allergen, and that leads to protection as long as people continue to take that therapy.

This is pretty effective in desensitizing an individual, so roughly 75% to 80% of individuals will respond to allergen immunotherapy. But the issue is that just like before, they always had to avoid the food. Now they always have to take their medication with taking this immunotherapy in order to maintain the protection that they get. So, it's not a cure.

In your paper, you discuss the need for more precision therapies for IgE-mediated allergies. Please describe these therapies.

One of them is an antibody called dupilumab, which binds to the IL-4 receptor, which is used by two different cytokines, IL-4 and IL-13. These play a very important role in allergic diseases. They are responsible for the B-cell making IgE antibodies, and so the idea is that by blocking those cytokines from binding to their receptors, you can reduce the amount of IgE and also reduce the effect of those cytokines on other aspects of physiology.

This has been tested in two ways. One is as a standalone therapy—giving anti-IL-4 and anti-IL-13—which has not proven to be particularly effective. The other, which is currently being tested, is combining this approach with giving the allergen. The benefit here is that the T-cell and the B-cells are getting activated, but they're getting starved of the cytokine IL-4 and IL-13. So, the idea is that you're going to reprogram the B-cell and the T-cell response because they're no longer getting those Th2 cytokines.

That is also the idea behind the use of JAK inhibitors. JAKs are part of the signaling cascade that is responsible for cytokine receptors having their effects on cells. They target more cytokine receptors than antibodies do. So, the idea is by blocking more cytokines that are involved in allergic disease, they may be more effective at their job.

The precision medicine part of this comes in because we had found in a previous clinical trial of oral immunotherapy that individuals who had a high frequency of Th2 cells—or type two T-cells in peripheral blood—were more likely to fail treatment. They weren't able to get up to the maintenance dose of therapy, and they were less likely to become fully desensitized. If it were possible to test ahead of time whether a patient has a high frequency of these cells, we could perhaps predict whether or not adding dupilumab or a JAK inhibitor to the oral immunotherapy might improve the odds of treatment success.

What are the next steps in food allergy research and treatment development?

I think that there are two key questions. First is identifying who could really benefit from adding on additional therapies. These broader therapies do have more side effects. Inhibiting more cytokines is going to have more side effects than being very targeted. It would be great if we could identify who would respond well to plain oral immunotherapy—then, we could say that they do not need to be exposed to more immunomodulation.

But we may be able to identify those who would respond well versus those who do not. We've also identified these type 2 T-cells. We know that with immunotherapy they get depleted, but when immunotherapy stops, they come back. From an immunology basic science perspective, we need to understand where the memory cells are that can repopulate those pathogenic Th2 cells. Can we prevent those Th2 cells from coming back after we've stopped therapy? That's something that I think still needs more research to understand.

More information: M. Cecilia Berin, Targeting type 2 immunity and the future of food allergy treatment, Journal of Experimental Medicine (2023). DOI: 10.1084/jem.20221104

Citation: The future of IgE-mediated allergy research and treatments (2023, March 30) retrieved 31 March 2023 from https://medicalxpress.Com/news/2023-03-future-ige-mediated-allergy-treatments.Html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.


What Is A Milk Protein Allergy? Symptoms, Causes And Treatment

Malina Malkani, M.S., R.D.N., C.D.N., is the registered dietitian, best-selling author and single mom of three behind the Instagram and TikTok account, @healthy.Mom.Healthy.Kids. She is a top nutrition influencer and trusted expert in local and national media outlets and publications including The Doctors (CBS), Everyday Health, Sirius XM Doctor Radio, Newsweek, Well + Good, Health, Insider, HuffPost, CNN and Food Network. Malina owns a nutrition consulting company and private practice (MalinaMalkani.Com), dedicated to helping parents feed their babies and kids with confidence. She is the author of Simple and Safe Baby-Led Weaning: How to Integrate Foods, Manage Portion Sizes and Identify Allergies and the creator of two online courses for parents called, Safe & Simple Baby-Led Feeding, and Solve Picky Eating. A former national media spokesperson for the Academy of Nutrition and Dietetics, she completed her undergraduate degrees at Northwestern University and master's degree in clinical nutrition at New York University. Currently, she works with companies including the following: Nature's Way KiDS, Lil Mixins Allergen Powders, Eztotz, Kvaroy Arctic Salmon, Active Skin Repair, Girl Factor, That's It!, Kalena Organic Sparkling Coconut Water, National Peanut Board, Danone North America, General Mills, Wakunaga, Purity Coffee, Egg Nutrition Center, Littlemore, Inc., Petit Pot, Else Nutrition, Force of Nature, Med-IQ, Robert Wood Johnson Foundation, Guiding Stars Nutrition, Mission MightyMe, Plum Organics, Stokke Baby, The Secret Life of Skin, Bio-First.


Antagonism Of The Prostaglandin D

  • Urade, Y. & Hayaishi, O. Prostaglandin D2 and sleep regulation. Biochim. Biophys. Acta 1436, 606–615 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Eguchi, N. Et al. Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice. Proc. Natl Acad. Sci. USA 96, 726–730 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis, R. A. Et al. Prostaglandin D2 generation after activation of rat and human mast cells with anti-IgE. J. Immunol. 129, 1627–1631 (1982).

    CAS  PubMed  Google Scholar 

  • Peters, S. P. Et al. The role of prostaglandin D2 in IgE-mediated reactions in man. Trans. Assoc. Am. Physicians 95, 221–228 (1982).

    CAS  PubMed  Google Scholar 

  • Urade, Y., Ujihara, M., Horiguchi, Y., Ikai, K. & Hayaishi, O. The major source of endogenous prostaglandin D2 production is likely antigen-presenting cells. Localization of glutathione-requiring prostaglandin D synthetase in histiocytes, dendritic, and Kupffer cells in various rat tissues. J. Immunol. 143, 2982–2989 (1989).

    CAS  PubMed  Google Scholar 

  • Tanaka, K. Et al. Differential production of prostaglandin D2 by human helper T cell subsets. J. Immunol. 164, 2277–2280 (2000).

    Article  CAS  PubMed  Google Scholar 

  • O'Sullivan, S., Dahlen, B., Dahlen, S. E. & Kumlin, M. Increased urinary excretion of the prostaglandin D2 metabolite 9α, 11β-prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction. J. Allergy Clin. Immunol. 98, 421–432 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Bochenek, G., Nagraba, K., Nizankowska, E. & Szczeklik, A. A controlled study of 9α, 11β-PGF2 (a prostaglandin D2 metabolite) in plasma and urine of patients with bronchial asthma and healthy controls after aspirin challenge. J. Allergy Clin. Immunol. 111, 743–749 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Dahlen, S. E. & Kumlin, M. Monitoring mast cell activation by prostaglandin D2 in vivo. Thorax 59, 453–455 (2004). An editorial on the utility of using the PGD 2 metabolite 9α11βPGF 2 as an in vivo marker of mast-cell activation in humans. 9α11βPGF 2 is a more sensitive marker of mast-cell activation than tryptase or histamine metabolites.

    Article  PubMed  PubMed Central  Google Scholar 

  • Murray, J. J. Et al. Release of prostaglandin D2 into human airways during acute antigen challenge. N. Engl. J. Med. 315, 800–804 (1986). One of the first studies to show that PGD 2 is produced rapidly and in high concentrations in response to an allergen in subjects with allergies.

    Article  CAS  PubMed  Google Scholar 

  • Naclerio, R. M. Et al. Mediator release after nasal airway challenge with allergen. Am. Rev. Respir. Dis. 128, 597–602 (1983).

    CAS  PubMed  Google Scholar 

  • Charlesworth, E. N., Kagey-Sobotka, A., Schleimer, R. P., Norman, P. S. & Lichtenstein, L. M. Prednisone inhibits the appearance of inflammatory mediators and the influx of eosinophils and basophils associated with the cutaneous late-phase response to allergen. J. Immunol. 146, 671–676 (1991).

    CAS  PubMed  Google Scholar 

  • Benyon, R. C., Robinson, C. & Church, M. K. Differential release of histamine and eicosanoids from human skin mast cells activated by IgE-dependent and non-immunological stimuli. Br. J. Pharmacol. 97, 898–904 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulman, E. S., Newball, H. H., Demers, L. M., Fitzpatrick, F. A. & Adkinson, N. F. Jr. Anaphylactic release of thromboxane A2, prostaglandin D2, and prostacyclin from human lung parenchyma. Am. Rev. Respir. Dis. 124, 402–406 (1981).

    CAS  PubMed  Google Scholar 

  • Naclerio, R. M. Et al. Inflammatory mediators in late antigen-induced rhinitis. N. Engl. J. Med. 313, 65–70 (1985).

    Article  CAS  PubMed  Google Scholar 

  • Hirai, H. Et al. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J. Exp. Med. 193, 255–261 (2001). A landmark paper demonstrating that CRTH2 mediates the effect of PGD 2 on T H 2 lymphocytes, eosinophils and basophils and that PGD 2 is the predominant CRTH2 agonist produced by mast cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gazi, L. Et al. Δ12-prostaglandin D2 is a potent and selective CRTH2 receptor agonist and causes activation of human eosinophils and Th2 lymphocytes. Prostaglandins Other Lipid Mediat. 75, 153–167 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Heinemann, A., Schuligoi, R., Sabroe, I., Hartnell, A. & Peskar, B. A. Δ12-prostaglandin J2, a plasma metabolite of prostaglandin D2, causes eosinophil mobilization from the bone marrow and primes eosinophils for chemotaxis. J. Immunol. 170, 4752–4758 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Monneret, G., Li, H., Vasilescu, J., Rokach, J. & Powell, W. S. 15-Deoxy-Δ12, 14-prostaglandins D2 and J2 are potent activators of human eosinophils. J. Immunol. 168, 3563–3569 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Sandig, H., Andrew, D., Barnes, A. A., Sabroe, I. & Pease, J. 9α, 11β-PGF2 and its stereoisomer PGF2α are novel agonists of the chemoattractant receptor, CRTH2. FEBS Lett. 580, 373–379 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Bohm, E. Et al. 11-dehydro-thromboxane B2, a stable thromboxane metabolite, is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and basophils. J. Biol. Chem. 279, 7663–7670 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Forman, B. M. Et al. 15-deoxy-Δ12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 83, 803–812 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Rossi, A. Et al. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 403, 103–108 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Ide, T., Egan, K., Bell-Parikh, L. C. & Fitzgerald, G. A. Activation of nuclear receptors by prostaglandins. Thromb. Res. 110, 311–315 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Flower, R. J., Harvey, E. A. & Kingston, W. P. Inflammatory effects of prostaglandin D2 in rat and human skin. Br. J. Pharmacol. 56, 229–233 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soter, N. A., Lewis, R. A., Corey, E. J. & Austen, K. F. Local effects of synthetic leukotrienes (LTC4, LTD4, LTE4, and LTB4) in human skin. J. Invest. Dermatol. 80, 115–119 (1983).

    Article  CAS  PubMed  Google Scholar 

  • Williams, T. J. & Peck, M. J. Role of prostaglandin-mediated vasodilatation in inflammation. Nature 270, 530–532 (1977).

    Article  CAS  PubMed  Google Scholar 

  • Giles, H., Leff, P., Bolofo, M. L., Kelly, M. G. & Robertson, A. D. The classification of prostaglandin DP-receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist. Br. J. Pharmacol. 96, 291–300 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodward, D. F. Et al. Studies on the ocular pharmacology of prostaglandin D2 . Invest. Ophthalmol. Vis. Sci. 31, 138–146 (1990). The first study to provide evidence that the effects of PGD 2 on eosinophil accumulation in vivo are not DP 1 -mediated.

    CAS  PubMed  Google Scholar 

  • Marsden, K. A., Rao, P. S., Cavanagh, D. & Spaziani, E. The effect of prostaglandin D2 (PGD2) on circulating eosinophils. Prostaglandins Leukot. Med. 15, 387–397 (1984).

    Article  CAS  PubMed  Google Scholar 

  • Emery, D. L., Djokic, T. D., Graf, P. D. & Nadel, J. A. Prostaglandin D2 causes accumulation of eosinophils in the lumen of the dog trachea. J. Appl. Physiol. 67, 959–962 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Fujitani, Y. Et al. Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice. J. Immunol. 168, 443–449 (2002). This study demonstrates that the overproduction of PGD 2 enhances allergic airway inflammation.

    Article  CAS  PubMed  Google Scholar 

  • Raible, D. G., Schulman, E. S., DiMuzio, J., Cardillo, R. & Post, T. J. Mast cell mediators prostaglandin-D2 and histamine activate human eosinophils. J. Immunol. 148, 3536–3542 (1992).

    CAS  PubMed  Google Scholar 

  • Monneret, G., Gravel, S., Diamond, M., Rokach, J. & Powell, W. S. Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor. Blood 98, 1942–1948 (2001). The first definitive study demonstrating that the effects of PGD 2 on eosinophil activation are mediated by a novel receptor.

    Article  CAS  PubMed  Google Scholar 

  • Nagata, K. Et al. Selective expression of a novel surface molecule by human Th2 cells in vivo. J. Immunol. 162, 1278–1286 (1999).

    CAS  PubMed  Google Scholar 

  • Nagata, K. Et al. CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s). FEBS Lett. 459, 195–199 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Coleman, R. A. & Sheldrick, R. L. Prostanoid-induced contraction of human bronchial smooth muscle is mediated by TP-receptors. Br. J. Pharmacol. 96, 688–692 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liston, T. E. & Roberts, L. J. Transformation of prostaglandin D2 to 9α, 11 β-(15S)-trihydroxyprosta-(5Z, 13E)-dien-1-oic acid (9α, 11β-prostaglandin F2): a unique biologically active prostaglandin produced enzymatically in vivo in humans. Proc. Natl Acad. Sci. USA 82, 6030–6034 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beasley, C. R. Et al. 9α, 11β-prostaglandin F2, a novel metabolite of prostaglandin D2 is a potent contractile agonist of human and guinea pig airways. J. Clin. Invest. 79, 978–983 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuoka, T. Et al. Prostaglandin D2 as a mediator of allergic asthma. Science 287, 2013–2017 (2000). This study examines the phenotype of the DP 1 -knockout mouse and demonstrates that DP 1 -receptor activation contributes to T H 2-cytokine production, eosinophil infiltration, mucus production and airway hyperresponsiveness in response to allergic challenge.

    Article  CAS  PubMed  Google Scholar 

  • Nantel, F. Et al. Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa. Prostaglandins Other Lipid Mediat. 73, 87–101 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Heavey, D. J. Et al. Effects of intravenous infusions of prostaglandin D2 in man. Prostaglandins 28, 755–767 (1984).

    Article  CAS  PubMed  Google Scholar 

  • Doyle, W. J., Boehm, S. & Skoner, D. P. Physiologic responses to intranasal dose–response challenges with histamine, methacholine, bradykinin, and prostaglandin in adult volunteers with and without nasal allergy. J. Allergy Clin. Immunol. 86, 924–935 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Johnston, S. L., Smith, S., Harrison, J., Ritter, W. & Howarth, P. H. The effect of BAY u 3405, a thromboxane receptor antagonist, on prostaglandin D2-induced nasal blockage. J. Allergy Clin. Immunol. 91, 903–909 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Arimura, A. Et al. Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751. J. Pharmacol. Exp. Ther. 298, 411–419 (2001).

    CAS  PubMed  Google Scholar 

  • Cheng, K. Et al. Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Proc. Natl Acad. Sci. USA 103, 6682–6687 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hammad, H. Et al. Prostaglandin D2 inhibits airway dendritic cell migration and function in steady state conditions by selective activation of the D prostanoid receptor 1. J. Immunol. 171, 3936–3940 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Faveeuw, C. Et al. Prostaglandin D2 inhibits the production of interleukin-12 in murine dendritic cells through multiple signaling pathways. Eur. J. Immunol. 33, 889–898 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Gosset, P. Et al. Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response. Eur. J. Immunol. 35, 1491–1500 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Tanaka, K., Hirai, H., Takano, S., Nakamura, M. & Nagata, K. Effects of prostaglandin D2 on helper T cell functions. Biochem. Biophys. Res. Commun. 316, 1009–1014 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Xue, L. Et al. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J. Immunol. 175, 6531–6536 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Gilroy, D. W. Et al. Inducible cyclooxygenase may have anti-inflammatory properties. Nature Med. 5, 698–701 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Ajuebor, M. N., Singh, A. & Wallace, J. L. Cyclooxygenase-2-derived prostaglandin D(2) is an early anti-inflammatory signal in experimental colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 279, G238–G244 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Trivedi, S. G. Et al. Essential role for hematopoietic prostaglandin D2 synthase in the control of delayed type hypersensitivity. Proc. Natl Acad. Sci. USA 103, 5179–5184 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugimoto, H. Et al. An orally bioavailable small molecule antagonist of CRTH2, ramatroban (BAY u3405), inhibits prostaglandin D2-induced eosinophil migration in vitro. J. Pharmacol. Exp. Ther. 305, 347–352 (2003). The first demonstration that ramatroban is an effective CRTH2 antagonist that inhibits PGD 2 -mediated eosinophil migration.

    Article  CAS  PubMed  Google Scholar 

  • McKenniff, M. G., Norman, P., Cuthbert, N. J. & Gardiner, P. J. BAY u3405, a potent and selective thromboxane A2 receptor antagonist on airway smooth muscle in vitro. Br. J. Pharmacol. 104, 585–590 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shichijo, M. Et al. Chemoattractant receptor-homologous molecule expressed on Th2 cells activation in vivo increases blood leukocyte counts and its blockade abrogates 13,14-dihydro-15-keto-prostaglandin D2-induced eosinophilia in rats. J. Pharmacol. Exp. Ther. 307, 518–525 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Narita, S., Asakura, K. & Kataura, A. Effects of thromboxane A2 receptor antagonist (Bay u 3405) on nasal symptoms after antigen challenge in sensitized guinea pigs. Int. Arch. Allergy Immunol. 109, 161–166 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Nagai, H. Et al. The effect of a thromboxane A2 receptor antagonist BAY-u-3405 on experimental allergic reactions. Prostaglandins 50, 75–87 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Takeshita, K. Et al. CRTH2 is a prominent effector in contact hypersensitivity-induced neutrophil inflammation. Int. Immunol. 16, 947–959 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Gyles S. L. Et al. A dominant role for chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) in mediating chemotaxis of CRTH2+CD4+ Th2 lymphocytes in response to mast cell supernatants. Immunology 119, 362–368 (2006). This study provides evidence that mast-cell-dependent activation of mast cells is mediated by PGD 2 acting on CRTH2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spik, I. Et al. Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse. J. Immunol. 174, 3703–3708 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Satoh, T. Et al. Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor. J. Immunol. 177, 2621–2629 (2006). A study demonstrating that allergic responses are diminished in CRTH2-knockout mice.

    Article  CAS  PubMed  Google Scholar 

  • Chevalier, E. Et al. Chemoattractant receptor-homologous molecule expressed on Th2 cells plays a restricting role on IL-5 production and eosinophil recruitment. J. Immunol. 175, 2056–2060 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Abe, H. Et al. Molecular cloning, chromosome mapping and characterization of the mouse CRTH2 gene, a putative member of the leukocyte chemoattractant receptor family. Gene 227, 71–77 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Williams, C. M. & Galli, S. J. Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J. Exp. Med. 192, 455–462 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Y. H. Et al. Maintenance and polarization of human Th2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity 24, 827–838 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Ying, S. Et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 174, 8183–8190 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Angeli, V. Et al. Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses. J. Immunol. 172, 3822–3829 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Hardy, C. C., Robinson, C., Tattersfield, A. E. & Holgate, S. T. The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. N. Engl. J. Med. 311, 209–213 (1984).

    Article  CAS  PubMed  Google Scholar 

  • Magnussen, H., Boerger, S., Templin, K. & Baunack, A. R. Effects of a thromboxane-receptor antagonist, BAY u 3405, on prostaglandin D2- and exercise-induced bronchoconstriction. J. Allergy Clin. Immunol. 89, 1119–1126 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Johnston, S. L. Et al. The effects of an oral thromboxane TP receptor antagonist BAY u 3405, on prostaglandin D2- and histamine-induced bronchoconstriction in asthma, and relationship to plasma drug concentrations. Br. J. Clin. Pharmacol. 34, 402–408 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beasley, R. C. Et al. Effect of a thromboxane receptor antagonist on PGD2- and allergen-induced bronchoconstriction. J. Appl. Physiol. 66, 1685–1693 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Rajakulasingam, K. Et al. Effect of thromboxane A2-receptor antagonist on bradykinin-induced bronchoconstriction in asthma. J. Appl. Physiol. 80, 1973–1977 (1996).

    Article  CAS  PubMed  Google Scholar 

  • al Jarad, N., Hui, K. P. & Barnes, N. Effects of a thromboxane receptor antagonist on prostaglandin D2 and histamine induced bronchoconstriction in man. Br. J. Clin. Pharmacol. 37, 97–100 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finnerty, J. P., Twentyman, O. P., Harris, A., Palmer, J. B. & Holgate, S. T. Effect of GR32191, a potent thromboxane receptor antagonist, on exercise induced bronchoconstriction in asthma. Thorax 46, 190–192 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coleman, R. A. GR32191 and the role of thromboxane A2 in asthma--preclinical and clinical findings. Agents Actions Suppl. 34, 211–220 (1991). This provides evidence that the TP-mediated bronchoconstrictor actions of PGD 2 and thromboxane A 2 do not make a significant contribultion to the manifestation of clincal asthma.

    Article  CAS  PubMed  Google Scholar 

  • Terada, N. Et al. The effect of ramatroban (BAY u 3405), a thromboxane A2 receptor antagonist, on nasal cavity volume and minimum cross-sectional area and nasal mucosal hemodynamics after nasal mucosal allergen challenge in patients with perennial allergic rhinitis. Acta Otolaryngol. Suppl. 537, 32–37 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Aizawa, H., Shigyo, M., Nogami, H., Hirose, T. & Hara, N. BAY u3405, a thromboxane A2 antagonist, reduces bronchial hyperresponsiveness in asthmatics. Chest 109, 338–342 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Kirby, J. G., Hargreave, F. E., Cockcroft, D. W. & O'Byrne, P. M. Effect of indomethacin on allergen-induced asthmatic responses. J. Appl. Physiol. 66, 578–583 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Raud, J., Dahlen, S. E., Sydbom, A., Lindbom, L. & Hedqvist, P. Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release. Proc. Natl Acad. Sci. USA 85, 2315–2319 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Comments

    Popular Posts

    Best Free LaTeX Editors for Windows 10 - TWCN Tech News

    Nationwide shortage of asthma medication albuterol could worsen in hospitals