IL-3, IL-5, IL-9 cytokine Crowe. biogenic amine, TTX proteoglycans, protease TNF-alpha. 13 lipid-derived mediator cytokines RMCPII. 14. cytokine

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1 Mast Cells in Functional Gastrointestinal Disorders Sei Jin Youn, M.D. Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea 서 론. (effector cell).. mucosal mast cell (MMC) connective. mast cell (CTMC)..,.. CTMC,,, MMC (immunocompetent cells).. 1,2 MMC (5-10µm) CTMC (10-20µm). MMC. histamine, 5-hydroxytryptamine (5-HT), rat. mast cell protease II (RMCP II), prostaglandins, leukotrienes platelet-activating factor(paf). 2 Tumor Necrosis, Factor(TNF)-alpha, interleukin(il)-1, -3, -4, -5, -6, GM-CSF, MCP-1 cytokines chemokines MMC.. IgE/antigen substance P acetylcholine 점막비만세포. 3,4,5 protease tryptase. 2. IgE- (. ) -IgE- (, ) cytokines. 2,6,7 TNF-alpha, 접수: 2005년 6월 2일 IL-1, -5, -8, -16, -18 cytokines 책임저자 : 윤세진, 충북청주시흥덕구개신동 62( ) 충북대학교의과대학내과학교실 mrna. stem cell factor Tel: (043) , 6357 Fax: (043) (SCF)-conditioned media IL-4 IgE-receptor SJYoun@chungbuk.ac.kr

2 IL-3, IL-5, IL-9 cytokine Crowe. biogenic amine, TTX proteoglycans, protease TNF-alpha. 13 lipid-derived mediator cytokines RMCPII. 14. cytokines TTX RMCPII 비만세포-신경-상피세포상호작용.. 스트레스에 의해 유발된상피기능장애모델. Nippostrongylus brasiliensis 67% ( water avoidance ) % (<1µm). 9 Newson. CL horseradish peroxidase ( ) endosomes.. 15 atropine 과민성모델 (Models of hypersensitivity). acetylcholine. 15,16 water avoidance stress,. 17. Castro T. spiralis worm antigen short-circuit current(isc) tetrodotoxin (TTX), atropine histamine 5-HT cold pain stress MMC prostaglandin E2 histamine tryptase, histamine, PG D HT. 11 기능성위장장애의 신경면역생리학적범례 Perdue. anti-ige TTX 50%,,

3 (paradoxical output).,,. - /.. serotonin, histamine, prostaglandins, leukotrienes, platelet-activating factor cytokines. (Fig. 1). histamine (Fig. 1). 21., Guinea pig. histamine (effector system) /.. 22, histamine.. 24,25.,, (propulsive histamine motor).. 기능성위장장애에서뇌-비만세포상호작용... 8,26,27 protease.. 20 Thyrotropin releasing hormone (TRH) -. 5 TRH cold-restraint stress. restraint stress histamine

4 . 28 corticotropin releasing factor (CRF) Compylobacter 25%. CRF. 34 CRF ,32, (, ),.. 38 (secretory behavior)... 21, I.,,,, / ( ). 31,36,39,.. 36,40 substance P.. substance P,. 36,41. PAR-2 (proteinase activated receptor 2), , 과민성장증후군에서비만세포. 33,34.

5 , (Fig. 2).. histamine, tryptase.,,. 44,45. 요 약, 42 Constantine substance P.. 43.,. /.. -.,,. -, 참고문헌 1. Crowe SE, Perdue MH. Gastrointestinal food hypersensitivity: basic mechanisms of pathophysiology. Gastroenterology 1992;103: Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev 1997;77: Shanahan F, Denburg JA, Fox J, Bienenstock J, Befus D. Mast cell heterogeneity: effects of neuroenteric peptides on histamine release. J Immunol 1985;135: Bani-Sacchi T. The release of histamine by parasympathetic stimulation in guinea-pig aurical and rat ileum. J Physiol 1986;371: Santos J, Saperas E, Mourelle M, Antolin M. Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats. Gastroenterology 1996;111:

6 6. Lorentz A, Schwengberg S, Sellge G, Manns MP, Bischoff SC. Human intestinal mast cells are capable of producing different cytokine profiles: role of IgE receptor cross-linking and IL-4. J Immunol 2000;164: Theoharides TC, Bondy PK, Tsakalos ND, Askenase PW. Differential release of serotonin and histamine from mast cells. Nature 1982;297: Stead RH, Tomioka M, Quinonez G, Simon GT, Felten SY, Bienenstock J. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. Proc Natl Acad Sci USA 1987;84: Stead RH, Dixon MF, Bramwell NH, Riddell RH, Bienenstock J. Mast cells are closely apposed to nerves in the human gastrointestinal mucosa.gastroenterology 1989;97: Newson B, Dahlstrom A, Enerback L, Ahlman H. Suggestive evidence for a direct innervation of mucosal mast cells. Neuroscience 1983;10: Castro GA, Harari Y, Russel D. Mediators of anaphylaxis-induced ion transport changes in small intestine. Am J Physiol 1987;253:G540-G Crowe SE, Perdue MH. Anti-immunoglobulin E-stimulated ion transport in human large and small intestine. Gastroenterology 1993;105: Crowe SE, Soda K, Stanisz AM, Perdue MH. Intestinal permeability in allergic rats: nerve involvement in antigen-induced changes. Am J Physiol 1993;264:G617-G Berin MC, Kiliaan AJ, Yang PC, Groot JA, Kitamura Y, Perdue MH. The influence of mast cells on pathways of transepithelial antigen transport in rat intestine. J Immunol 1998;161: Kiliaan AJ. Stress stimulates transepithelial macromolecular uptake in rat jejunum. Am J Physiol 1998;275:G1037-G Saunders PR, Hanssen NPM, Perdue MH. Cholinergic nerves mediate stress-induced intestinal transport abnormalities in Wistar-Kyoto rats. Am J Physiol 1997;273:G486-G Santos J, Benjamin M, Yang PC, Prior T, Perdue MH. Chronic stress impairs rat growth and jejunal epithelial barrier function: role of mast cells. Am J Physiol 2000;278:G847-G Theoharides TC. Stress-induced rat intestinal mast cell intragranular activation and inhibitory effect of sulfated proteoglycans. Dig Dis Sci 1999;44:87S-93S. 19. Wilson LM, Baldwin AL. Environmental stress causes mast cell degranulation, endothelial and epithelial changes, and edema in the rat intestinal mucosa. Microcirculation 1999;6: Santos J. Release of mast cell mediators into the jejunum by cold pain stress in humans. Gastroenterology 1998;114: JD Wood, DH Alpers, PLR Andrews. Fundermentals of neuroga stroenterology Gut 1999;45(supplII):II6-II16). 22. Wood JD. Neuro-immunophysiolgy of colon function. Pharmacology 1993;47(suppl 1): Phillips SF. Motility disorders of the colon. In: Yamada T, Alpers DH, Owyang C. eds. Textbook of gastroenterology. Philadelphia: JB Lippincott, 1995; Frieling T, Cooke HJ, Wood JD. Neuroimmune communication in the submucous plexus of guinea-pig colon after sensitization to milk antigen. Am J Physiol 1994;267:G1087-G Frieling T, Palmer JM, Cooke HJ. Neuroimmune communication in the submucous plexus of guinea pig colon after infection with Trichinella spiralis. Gastroenterology 1994;107: Williams RM, Berthoud HR, Stead RH. Association between vagal afferent nerve fibers and mast cells in rat jejunal mucosa [abstract]. Gastroenterology 1995;108:A Gottwald T, Lhotak S, Stead R. Effect of truncal vagotomy and capsaicin on mast cells and IgA-positive plasma cells in rat jejunal mucosa. Neurogastroenterol Motil 1997;9: Gue M, Del Rio-Lacheze C, Eutamene H. Stress-induced visceral hypersensitivity to rectal distension in rats: role of CRF and mast cells. Neurogastroenterol Motil 1997;9: Coelho AM, Fioramonti J, Bueno L. Mast cell degranulation induces delayed rectal allodynia in rats: role of histamine and 5-HT. Dig Dis Sci 1998;43: Park HJ. Postinfectious irritable bowel syndrome. Korean J Gastrointestinal Motil 2002;8: Maxwell PR, Mendall MA, Kumar D. Irritable bowel syndrome. Lancet 1997;350: Horwitz BJ, Fisher RS. Current concepts: the Irritable Bowel Syndrome. NEJM 2001;344: Collins SM, Vallance B, Barbara G, Borgaonkar M. Putative inflammatory and immunological mechanisms in functional bowel disorders. Bailliere's Clinical Gastroenterology 1999;13: Bischoff SC. Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut. Baillieres Clin Gastroenterol 1996;10: Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysentery irritable bowel syndrome. Gut 2000;47: Weston AP, Biddle WL, Bhatia PS, Miner PB Jr. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci 1993;38: O'Sullivan M, Clayton N, Breslin NP, et al. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil 2000;12: JH Choi, BK Nah, JM Leem, SS Bae, KW Choi, HB Chai, SM Park, SJ Youn, R Sung. Mucosal mast cells in irritable bowel syndrome. Kor J Neurogastroenterol Motil 2004;10: Gui, Xian-Yong. Mast cells: a possible link between psychological stress, enteric infection, food allergy and gut hypersensitivity in the irritable bowel syndrome. J Gastroenterol Hepatol 1998;13: Bischoff SC, Mayer JH, Manns MP. Allergy and the gut. Int Arch Allergy Immunol 2000;121: Bauer O, Razin E. Mast cell-nerve interactions. News Physiol Sci 2000;15: Moriarty D, Selve N, Baird AW, Goldhill J. Potent NK1 antagonism by SR reduces rat colonic secretory response to immunocyte activation. Am J Physiol Cell Physiol 2001;280: Gue M, Rio-Lacheze CD, Eutamene H, Theodorou V, Fioramonti J, Bueno L. Stress-induced visceral hypersensitivity to rectal distension in rats:role of CRF and mast cells. Neurogastroenterol Motil 1997;9: Constantine S, Xinzhu P, Konstantinos L. Stress-induced bladder mast cell activation: implications for interstitial cystitis. J Urology 1997;157: Giovanni Barbara, Vincenzo Stanghellini, Roberto De Giorgio, Cesare Cremon, Graeme S. Cottrell, Donatella Santini, Gianandrea Pasquinelli, Antonio M. Morselli-Labate, Eileen F. Grady, Nigel W. Bunnett, Stephen M. Collins, Roberto Corinaldesi. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.2004;126: CH Park, YE Joo, SK Choi, JS Rew, SJ Kim, MC Lee. Activated mast cell infiltrate in close proximity to enteric nerves in diarrheapredominant irritable bowel syndrome. J Korean Med Sci 2003;18:

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ÀÇÇÐ°�ÁÂc00Ì»óÀÏ˘ Common Allergic Diseases in Children Sang - Il Lee, M.D. Department of pediatrics Sungkyunkwan University School of Medicine, Samsung Medical Center E - mail : silee@smc.samsung.co.kr Abstract Allergy