MorphologyMorphologyМорфология1026-35432949-2556Eco-Vector39947810.17816/morph.399478ArticlesСтатьиTISSUE AND CELL INTERACTIONSIN THE ORAL MUCOSA AFTER CYTOSTATICDRUGS ADMINISTRATIONТКАНЕВЫЕ И КЛЕТОЧНЫЕ ВЗАИМОДЕЙСТВИЯ В СЛИЗИСТОЙ ОБОЛОЧКЕ ПОЛОСТИ РТА ПРИ ВВЕДЕНИИ ЦИТОСТАТИКОВBykovV LБыковВ Л

Кафедра гистологии, цитологии и эмбриологии (зав. - проф. В.Л. Быков); Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова

Leont'evaI VЛеонтьеваИ В

Кафедра гистологии, цитологии и эмбриологии (зав. - проф. В.Л. Быков); Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова

BykovV LLeontiyevaI VСанкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова150920111393NO3 (2011)№3 (2011)71809052023Copyright ©; 2011, Eco-VectorCopyright ©; 2011, Эко-Вектор2011Eco-VectorЭко-Векторhttps://j-morphology.com/1026-3543/article/view/399478

In the preceding work («Morphology», 2011, issue 2), the regularities of oral mucosal (OM) epithelium injury after the cytostatic drug (CSD) treatment and its further regeneration, were reviewed. This paper presents the systematized summary of current literature data and the authors' own findings on the regularities of CSD effect on non-epithelial OM cell populations and their interactions with each other and the epithelium. The changes of intraepithelial tissue homeostasis, associated with CSD effect on intraepithelial lymphocytes, granulocytes, dendritic antigen presenting cells and melanocytes, interacting with epitheliocytes, are described. The data are presented, indicating that along with the epithelium, the cell populations of lamina propria and submucosal connective tissue, as well as the small blood vessels, are important targets of CSD in the OM tissues. The concept of a unifying model, describing tissue, cellular and molecular mechanisms of the oral mucositis development after CSD treatment, is reviewed.

В предшествующей работе («Морфология», 2011, вып. 2) проанализированы закономерности повреждения и регенерации покровного эпителия слизистой оболочки полости рта (СОПР) при воздействии цитостатиков (ЦС). В настоящей статье обобщены данные современной литературы и собственных наблюдений авторов о закономерностях влияния ЦС на неэпителиальные клеточные популяции СОПР и их взаимодействия друг с другом и с эпителием. Рассмотрены изменения внутритканевого гомеостаза эпителия, связанные с влиянием ЦС на взаимодействующие с эпителиоцитами внутриэпителиальные лимфоциты, гранулоциты, дендритные антиген-представляющие клетки и меланоциты. Приведены сведения, показывающие, что, наряду с эпителием, важнейшей мишенью ЦС в СОПР являются клеточные популяции соединительной ткани собственной пластинки и подслизистой основы, а также мелкие кровеносные сосуды. Рассмотрены представления о единой модели, описывающей тканевые, клеточные и молекулярные механизмы развития мукозита полости рта при введении ЦС.

oral cavityoral mucosaregenerationmucositiscytostatic drugsполость ртаслизистая оболочкарегенерациямукозитцитостатикиАкопян О.Г. Влияние высокодозной химиотерапии на слизистую оболочку полости рта у больных гемобластозами: Автореф. дис. …канд. мед. наук. М., 1997.Быков В.Л. Патогенез и морфогенез кандидоза при иммунодепрессии. Арх. пат., 1990, т. 52, № 11, с. 67-70.Быков В.Л. Динамика инвазивного роста Candida albicans в тканях хозяина. Вестн. дерматол. венерол., 1990, № 4, с. 25-28.Быков В.Л. Тканевые и клеточные защитные механизмы слизистой оболочки полости рта. Морфология, 1996, т. 110, вып. 6, с. 14-24.Быков В.Л. Дендритные антигенпредставляющие клетки слизистой оболочки полости рта в норме и при патологических состояниях. Арх. пат.,1997, т. 59, № 2, с. 71-75.Быков В.Л. Функциональная морфология эпителиального барьера слизистой оболочки полости рта. Стоматология, 1997, № 2, с. 15-20.Быков В.Л. Секреторные механизмы и секреторные продукты тучных клеток. Морфология, 1999, т. 115, вып. 2, с. 64-72.Быков В.Л. Иммунокомпетентные клетки десны человека в норме и при воспалительных заболеваниях пародонта. Арх. пат., 2005, т. 67, № 2, с. 51-55.Быков В.Л. Гистология и эмбриология органов полости рта. 3-е изд. СПб., Сотис, 2008.Быков В.Л. и Леонтьева И.В. Повреждение и репаративная регенерация эпителия слизистой оболочки полости рта при воздействии цитостатиков (тканевые, клеточные и молекулярные механизмы). Морфология, 2011, т. 139, вып. 2, с. 7-17.Быков В.Л., Леонтьева И.В. и Исеева Е.А. Морфофункциональные изменения эпителиев слизистой оболочки полости рта и пищевода при воздействии цитостатика. Морфология, 2010, т. 137, вып. 4, с. 42-43.Быков В.Л. и Пахомова Е.Н. Морфогенез кандидоза слизистых оболочек при введении иммунодепрессантов. Арх. пат.,1990, т. 52, № 1, с. 28-31.Исеева Е.А. и Быков В.Л. Морфофункциональные изменения пищевода при воздействии цитостатика. Морфология, 2006, т. 130, вып. 6, с. 62-67.Леонтьева И.В. Реакция тучных клеток и сосудистого русла слизистой оболочки полости рта на введение цитостатика. Морфология, 2010, т. 137, вып. 4, с. 113.Леонтьева И.В. и Быков В.Л. Реакция системы тучных клеток слизистой оболочки полости рта на введение цитостатиков. Учен. записки СПбГМУ им. И.П. Павлова, 2010, т. 17, № 4, с. 34-38.Леонтьева И.В. и Быков В.Л. Морфофункциональная характеристика эпителия слизистой оболочки полости рта при введении цитостатика и после его отмены. Морфология, 2011, т. 139, вып. 1, с. 52-59.Пахомова Е.Н. и Быков В.Л. Взаимодействие макрофагов с Candida albicans при иммунодепрессии. Журн. микробиол., 1994, № 1, с. 14-16.Пахомова Е.Н., Полякова М.И., Быков В.Л. и Караев З.О. Влияние цитостатиков и кортикостероидов на фагоцитарную и фунгицидную активность нейтрофильных гранулоцитов. Журн. микробиол., 1991, № 2, с. 66-68Adrian R.M., Hood A.F. and Skarin A.T. Mucocutaneous reactions to antineoplastic agents. CA Cancer J. Clin., 1980, v 30, p. 143-157.Ailor S.K. and Miles S.C. Dermatologic toxicity (Chapter 15). In: The Chemotherapy Source Book. 4th ed. Philadelphia, Lippincott Williams & Wilkins, 2008, p. 136-147.Akpek G., Knight R.D. and Wright D.G. Use of oral mucosal neutrophil counts to detect the onset and resolution of profound neutropenia following high-dose myelosuppressive chemotherapy. Am. J. Hematol., 2003, v. 72, № 1, p. 13-19.Ali A. and Mehta S. Alopecia. In: Medical Care of Cancer Patients.. Chapter 63. Shelton (CT), BC Decker Inc., 2009, p. 602-609.Allam J.P., Stojanovski G., Friedrichs N. et al. Distribution of Langerhans cells and mast cells within the human oral mucosa: new application sites of allergens in sublingual immunotherapy? Allergy, 2008, v. 63, № 6, p. 720-727.Baker D.G. The radiobiological basis for tissue reactions in the oral cavity following therapeutic x-irradiation. A review. Arch. Otolaryngol., 1982, v. 108, p. 21-24.Barrett A.P. Clinical characteristics and mechanisms involved in chemotherapy-induced oral ulceration. Oral Surg. Oral Med. Oral Pathol., 1987, v. 63, 4, p. 424-428.Barrett A.W., Cruchley A.T. and Williams D.M. Oral mucosal Langerhans' cells. Crit. Rev. Oral Biol. Med., 1996, v. 7, № l, p. 36-58.Bernhardson B.M., Tishelman C. and Rutqvist L.E. Chemosensory changes experienced by patients undergoing cancer chemotherapy: a qualitative interview study. J. Pain Symptom Managl., 2007, v. 34, № 4, p. 403-412.Blijlevens N.M.A., Donnelly J.P. and De Pauw B.E. Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant., 2000, v. 25, p. 1269-1278.Bronson R.E., Treat J.A. and Bertolami C.N. Fibroblastic subpopulations in uninjured and wounded rabbit oral mucosa. J. Dent. Res., 1989, v. 68, № 1, p. 51-58.Bültzingslöwen I., Carlsson G., Gustavsson B. and Jontell M. Effects of 5-fluorouracil on mitogen-induced costimulatory capacity of accessory cells from rat oral mucosa and dental pulp. J. Oral Pathol. Med., 2001, v. 30, № 6, p. 362-367.Bültzingslöwen I. and Jontell M. Macrophages, dendritic cells and T lymphocytes in rat buccal mucosa and dental pulp following 5-fluorouracil treatment. Eur. J. Oral Sci., 1999, v. 107, № 3, p. 194-201.Bykov V.L. Velocity of Candida albicans invasion into host tissues. Mycoses, 1991, v. 34, p. 293-296.Canady J.W., Johnson G.K and Squier C.A. Measurement of blood flow in the skin and oral mucosa of the rhesus monkey (Macaca mulatta using laser doppler flowmetry. Comp. Biochem. Physiol. (Part A: Physiology), 1993, v. 106, № 1, p. 61-63.Chiang C.P., Wu H.Y., Liu B.Y. et al. Quantitative analysis of immunocompetent cells in oral submucous fibrosis in Taiwan. Oral Oncol., 2002, v. 38, № 1, p. 56-63.Colasante A., Rosini S., Piattelli A. et al. Distribution and phenotype of immune cells in normal human gingiva: active immune response versus unresponsiveness. J. Oral Pathol. Med., 1992, v. 21, p. 12-16.Cutler C.W. and Jotwani R. Dendritic cells at the oral mucosal interface. J. Dent. Res., 2006, v. 85, № 8, p. 678-689.de Koning B.A.E., van Dieren J.M., Lindenbergh-Kortleve D.J. et al. Contributions of mucosal immune cells to methotrexateinduced mucositis. Int. Immunol., 2006, v. 18, № 6, p. 941-949.Delima A.J. and Van Dyke T.E. Origin and function of the cellular components in gingival crevice fluid. Periodontol 2000, 2003, v. 31, p. 55-76.Enoch S., Peake M.A., Wall I. et al.'Young' oral fibroblasts are geno/phenotypically distinct. J. Dent. Res., 2010, v. 89, № 12, p. 1407-1413.Farahani S.S., Navabazam A. and Ashkevari F.S. Comparison of mast cells count in oral reactive lesions. Pathol. Res. Pract., 2010, v.206, № 3, p. 151-155.Figdor C.G. Molecular characterization of dendritic cells operating at the interface of innate of acquired immunity. Pathol. Biol., 2003, v.51, p. 61-63.Förtsch D., Röllinghoff M. and Stenger S. IL-10 converts human dendritic cells into macrophage-like cells with increased antibacterial activity against virulent Mycobacterium tuberculosis. J. Immunol., 2000, v. 165, p. 978-987.Gibson R.J., Bowen J.M. and Keefe D.M.K. Technological advances in mucositis research: New insights and new issues. Cancer Treat. Rev., 2008, v. 34, p. 476-482.Gibson R.J., Cummins A.G., Bowen J.M. et al. Apoptosis occurs early in the basal layer of the oral mucosa following cancer chemotherapy. Asia-Pac. J. Clin. Oncol., 2006, v. 2, p. 39-49.Graham G.J., Ramenghi U., O'Connor M.P. et al. Studies of oral neutrophil levels in patients receiving G-CSF after autologus marrow transplantation. Br. J. Haematol., 1992, v. 82, p. 589-595.Guillot B., Bessis D. and Dereure O. Mucocutaneous side effects of antineoplastic chemotherapy. Expert Opin. Drug Saf., 2004, v. 3, № 6, p. 579-587.Hassell T.M. and Stanek E.J. Evidence that healthy human gingiva contains functionally heterogeneous fibroblast subpopulations, Arch. Oral Biol., 1983, v. 28, p. 617-625.Jotwani R. and Cutler C.W. Multiple dendritic cell (DC) subpopulations in human gingiva and association of mature dendritic cells with CD4+T-cells in situ. J. Dent. Res., 2003, v. 82, p. 736-741.Kamil N., Kamil S, Ahmed S.P. et al. Toxic effects of multiple anticancer drugs on skin. Pak. J. Pharm. Sci., 2010, v. 23, № 1, p. 7-14.Klein-Szanto A.J. and Schroeder H.E. Architecture and density of the connective tissue papillae of the human oral mucosa. J. Anat., 1977, v. 123, Pt. 1, p. 93-109.Koppel R.A and Boh E.E. Cutaneous reactions to chemotherapeutic agents. Am. J. Med., Sci., 2001, v. 321, p. 327-335.Lalla R.V., Peterson D.E., Brennan M.T. and Schubert M.M. Oral Toxicity. In: The Chemotherapy Source Book.4th Edn. Philadelphia, Lippincott Williams and Wilkins, 2008, p. 115-135.Lalla R.V., Sonis S.T. and Peterson D.E. Management of oral mucositis in patients who have cancer. Dent. Clin. North. Am., 2008, v. 52, № 1, p. 61-77.Lebendiger M. and Lehner T. Characterization of mononuclear cells in the human oral mucosa. Arch. Oral Biol., 1981, v. 26, № 12, p. 1041-1049.Lee H.G. and Eun H.C. Differences between fibroblasts cultured from oral mucosa and normal skin: implication to wound healing. J. Dermatol. Sci., 1999, v. 21, p. 176-182.Leitão R.F.C., Ribeiro R.A., Bellaguarda E.A.L. et al. Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster. Cancer Chemother. Pharmacol., 2007, v. 59, p. 603-612.Lieschke G.J., Ramenghi U., O'Connor M.P. et al. Studies of oral neutrophil levels in patients receiving G-CSF after autologous marrow transplantation. Br. J. Haematol., 1992, v. 82, p. 589-595.Lindhe J., Karring T. and Araujo M. Anatomy of the periodontium. In: Clinical Periodontology and Implant Dentistry. Oxford, Blackwell Munksgaard, 2003, p. 3-49.Lockhart P.B. and Sonis S.T. Relationship of oral complications to peripheral blood leukocyte and platelet counts in patients receiving cancer chemotherapy. Oral Surg. Oral Med. Oral Pathol., 1979, v. 48, № 1, p. 21-28.Lockhart P.B. and Sonis S.T. Alterations in the oral mucosa caused by chemotherapeutic agents. A histologic study. J. Dermatol. Surg. Oncol., 1981, v. 7, № 12, p. 1019-1025.Logan R.M. The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. PhD Thesis, The University of Adelaide, Australia, 2008.Logan R.M., Gibson R.J., Bowen J.M. et al. Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother. Pharmacol., 2008, v. 62, p. 33-41.Logan R.M., Gibson R.J., Sonis S.T. and Keefe D.M.K. Nuclear factor-kappaB (NFkB and cyclooxygenase-2 (COX-2 expression in the oral mucosa following cancer chemotherapy. Oral Oncol., 2007, v. 43, p. 395-401.Logan R.M., Stringer A.M., Bowen J.M. et al. The role of proinflammatory cytokines in cancer treatment-induced alimentary tract mucositis: Pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev., 2007, v. 33, № 5, p. 448-460.Logan R., Stringer A., Bowen J.M. et al. Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered? Cancer Chemother. Pharmacol., 2009, v. 63, p. 239-251.Lombardi T., Hauser C. and Budtz-Jorgensen E. Langerhans cells: structure, function, and role in oral pathological conditions. J. Oral Patho1. Med., 1993, v. 22, p. 193-202.Mackal C.L. T-cell immunodeficiency following cytotoxic antineoplastic therapy: a review. The Oncologist, 1999, v. 4, p. 370-378.Mackintosh J.A. The antimicrobial properties of melanocytes, melanosomes and melanin and the evolution of black skin. J. Theor. Biol., 2001, v. 211, № 2, p. 101-113.Manakova S., Puttonen K.A., Raasmaja A. et al. Ara-C induces apoptosis in monkey fibroblast cells. Toxicol. In Vitro., 2003, v. 17, p. 367-673.McElroy T.H. Infection in the patient receiving chemotherapy for cancer: oral considerations. J. Am. Dent. Assoc., 1984, v. 109, № 3, p. 454-456.Milstein D.M., te Boome L.C., Cheung Y.W. et al. Use of sidestream dark-field (SDF imaging for assessing the effects of high-dose melphalan and autologous stem cell transplantation on oral mucosal microcirculation in myeloma patients. Oral. Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 2010, v. 109, № 1, p. 91-97.Morelli J.G. and Norris D.A. Influence of inflammatory mediators and cytokines on human melanocyte function. J. Invest. Dermatol., 1993, v.100, 2 Suppl., p. 191S-195S.O'Brien S.N., Blijlevens N.M.A., Mahfouz T.H. and Anaissie E.J. Infections in patients with hematological cancer: recent developments. In: Hematology Am. Soc. Hematol. Educ. Program, 2003, p. 438-472.Paris F., Fuks Z., Kang A. et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science, 2001, v. 293, № 5528, p. 293-297.Person P., Stahl S.S., Crossley M.L. and Allison J.B. Histologic response of rat oral tissues to nonoral tumor growth and to cancer chemotherapeutic agents. II. Tongue, salivary glands, and oral mucosa. Oral Surg. Oral Med. Oral Pathol., 1957, v.10, p. 1075-1080.Pistorius A., Willershausen B. and Callaway A. Effects of selected immunosuppressive drugs on prostaglandin release, protein synthesis and cell proliferation in human gingival fibroblasts and on the growth of plaque bacteria. Eur. J. Med. Res., 2003, v. 8, № 1, p. 25-32.Puxeddu A., Piliponsky M., Bachelet I. and Levi-Schaffer F. Mast cells in allergy and beyond. Int. J. Biochem. Cell Biol., 2003, v. 35, № 12, p. 1601-1607.Rao S.P., Potnis A.V., Sobrinho T.C. et al: Pigmentation of the tongue after treatment with adriamycin. Cancer Treat. Rep., 1976, v. 60, p. 1402-1404.Renggli H.H. Phagocytosis by crevicular neutrophils. In: The Borderland Between Caries and Periodontal Disease. London, Acad. Press, 1977, p. 211-222.Schenk P. Melanocyten, Langerhanssche und Merkelsche Zellen in oralen Epithelien. Acta Otolaryngol., 1975, Bd. 80, № 3-4, S. 301-311.Schiött C.R. and Löe H. The origin and variation in number of leukocytes in the human saliva. J. Periodontal. Res., 1970, v. 5, p. 36-41.Scully C. Phagocytic and killing activity of human blood, gingival crevicular, and salivary polymorphonuclear leukocytes for oral streptococci. J. Dent. Res., 1982, v. 61, № 5, p. 636-639.Sonis S.T. Oral complications. In: Cancer Medicine. Baltimore, Lippincott, 1997, p. 3255-3264.Sonis S.T. Mucositis as a biological process-a new hypothesis for the development of chemotherapy induced stomatotoxicity. Oral Oncol., 1998, v. 34, p. 39-43.Sonis S.T. The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit. Rev. Oral Biol. Med., 2002, v. 13, № 5, p. 380-389.Sonis S.T. The pathobiology of mucositis. Nat. Rev. Cancer, 2004, v. 4, № 4, p. 277-284.Sonis S.T. New thoughts on the initiation of mucositis. Oral Dis., 2010, v. 16, № 7, p. 597-600.Sonis S.T., Elting L.S., Keefe D. et al. Perspectives on cancer therapy-induced mucosal injury. Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer, 2004, v. 100 (Suppl.), № 9, p. 1995-2025.Sonis S.T., Peterson R.L., Edwards L.J. et al. Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters. Oral Oncol., 2000, v. 36, № 4, p. 373-381.Sonis S.T., Tracey C., Shklar G. et al. An animal model for mucositis induced by cancer chemotherapy. Oral Surg. Oral Med. Oral Pathol., 1990, v. 69, p. 437-443.Squier C.A. and Hill M.W. Oral Mucosa. In: Oral Histology: Development, Structure and Function. 4th edn. St. Louis, Mosby-Year Book Inc, 1994, p. 389-431.Squier C.A. and Nanny D. Measurement of blood flow in the oral mucosa and skin of the rhesus monkey using radiolabelled microspheres. Arch. Oral Biol., 1985, v. 30, № 4, p. 313-318.Stefanelli C., Tantini B., Fattori M. et al. Caspase activation in etoposide-treated fibroblasts is correlated to ERK phosphorylation and both events are blocked by polyamine depletion. FEBS Lett., 2002, v. 527, p. 223-228.Susser W.S., Whitaker-Worth D.L. and Grant-Kels J.M. Mucocutaneous reactions to chemotherapy. J. Am. Acad. Dermatol., 1999, v. 40, № 3, p. 367-398.Tsatmali M., Ancans J. and Thody A.J. Melanocyte function and its control by melanocortin peptides. J. Histochem. Cytochem., 2002, v. 50, p. 125-133.Vancoillie G., Lambert J. and Nayaert J.M. Melanocyte biology and its implications for the clinician. Eur. J. Dermatol., 1999, v. 9, № 3, p. 241-251.van Loon L.A., Krieg S.R., Davidson C.L. and Bos J.D. Quantification and distribution of lymphocyte subsets and Langerhans cells in normal human oral mucosa and skin. J. Oral Pathol. Med., 1989, v. 18, p. 197-201.Walker D.M. Oral mucosal immunology: an overview. Ann. Acad. Med. Singapore, 2004, v. 33 (Suppl.), p. 27S-30S.Walsh L.J. Mast cells and oral inflammation. Crit. Rev. Oral Biol. Med., 2003, v. 14, № 3, p. 188-198.Walsh L.J., Kaminer M.S. and Lazarus G.S. Role of laminin in localization of human dermal mast cells. Lab. Invest., 1991, v. 65, p. 433-440.Watts M.E., Woodcock M., Arnold S. and Chaplin D.J. Effects of novel and conventional anti-cancer agents on human endothelial permeability: influence of tumour secreted factors. Anticancer Res., 1997, v. 17, p. 71-75.Wertz P.W. and Squier C.A. Cellular and molecular basis of barrier function in oral epithelium. Crit. Rev. Ther. Drug Carrier Syst., 1991, v. 8, № 3, p. 237-269.Willoughby S.G., Hopps R.M. and Johnson N.W. Changes in the rate of epithelial proliferation of rat oral mucosa in response to acute inflammation induced by turpentine. Arch. Oral Biol., 1986, v. 31, № 3, p. 193-199.Wright D.G., Meierovics A.I. and Foxley J.M. Assessing the delivery of neutrophils to tissues in neutropenia. Blood, 1986, v. 67, p. 1023-1030.Wymenga A.N., van der Graaf W.T., Hofstra L.S. et al. Phase I study of transforming growth factor-beta 3 mouthwashes for prevention of chemotherapy induced mucositis. Clin. Cancer Res., 1999, v. 5, p. 1363-1368.Wymenga A.N., van der Graaf W.T., Spijkervet F.L. et al. A new in vitro assay of quantitation of chemotherapy induced mucositis. Br. J. Cancer, 1997, v. 8, p. 1062-1066.