Problems of Radiation Medicine and Radiobiology

M. V. Krasnoselsky, L. I. Simonova, V. Z. Gertman, E. S. Pushkar, T. S. Zavadskaya

SI «Institute of Medical Radiology named by S.P. Grigoriev National Academy of Medical Sciences of Ukraine», 82 Pushkinska St., 61024, Kharkiv, Ukraine

TISSUE IMMUNE CELLS AND THEIR ROLE IN THE HEALING PROCESS OF INFECTED RADIATION ULCERS UNDER THE IMPACT OF PHOTODYNAMIC THERAPY (EXPERIMENTAL STUDY)

Objective. to study the effect of antibacterial photodynamic therapy (PDT) on the dynamics of tissue neutrophilic leukocytes CD18 and tissue macrophages ED1 in the tissues of infected radiation ulcer during the stages of spontaneous healing and in the treatment of PDT.
Materials and methods. Infected radiation ulcer was modeled by local X-ray irradiation of the rat thigh skin at a dose of 85.0 Gy, followed by applying to the surface of the ulcer bacterial suspension of S. аureus. PDT was performed using a «Barva-LED/630» photonic apparatus and a methylene blue photosensitizer. The effect of PDT on the state of cellular immunity was determined using an immunohistochemical method based on the quantitative indices of neutrophilic leukocytes CD18 and ED1 macrophages during the stages of healing of an infected radiation ulcer.
Results. In the course of spontaneous healing of the ulcer (control I), the dynamics of changes in the relative volume of tissue neutrophil leukocytes CD18 and ED1 macrophages in the lesion zone, a decrease in the CD18 / ED1 index more than 2 times indicated that switching of the neutrophil response to macrophage occurred before 52^nd days of observations. When infected with S. аureus X-ray (control II), the switching of the neutrophil response to the macrophage did not occur during the entire observation period. When using PDT in the case of S. аureus infected ulcer (experimental group), the decrease in the CD18 / ED1 index was determined from the 21^st day of observation.
Conclusions. The positive effect of the antibacterial PDT method of infected S. аureus radiation ulcers was manifested by complete microbial decontamination of the wound, reduction of phases of the wound process, complete healing of radiation ulcers.The use of PDT has led to the death of bacteria, a decrease in the number of neutrophilic leukocytes and an increase in macrophages in the lesion area, the switching of the neutrophilic response to the reaction of monocyte-macrophage cells in the early stages of healing.
Key words: photodynamic therapy, photosensitizer, photodiodes, infected radiation ulcers.

Problems of Radiation Medicine and Radiobiology.
2019;24:250-260. doi: 10.33145/2304-8336-2019-24-250-260

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1. Chereshnev VA, Litvitsky PF, Tsygan VN. [Clinical pathophysiology: a course of lectures]. 2nd ed. St. Petersburg: SpetsLit; 2015. 472 p. Russian.

2. Mayansky DN. [Chronic inflammation]. Moscow: Medicina; 1991. 272 p. Russian.

3. Schymeinsky J, Mocsai A, Walzog B. Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications. Thromb Haemost. 2007;98(2):262-73.

4. Roos D, Law SK. Hematologically important mutations leukocyte adhesion deficiency. Blood Cells Mol Dis. 2003;27(6):1000-4.

5. Lapchenko AS. [Photodynamic therapy. Fields of application and development prospects in otorhinolaryngology]. Vestnik otorinolaringologii. 2015;80(6):4-9. Russian.

6. Heinitz AV, Sorokaty AE, Yagudaev DM, Tukhmanov RS [Photodynamic therapy] Method creation history and mechanisms]. Lasernaya meditsina 2007;11(3):42-6.

7. Kapinus VN, Kaplan MA, Spichenkova IS., Shubina AM, Yaroslavtseva-Isaeva EV. [Photodynamic therapy of epithelial malignant neoplasms of the skin]. Fotodinamicheskaya terapiya i fotodiagnostika.. 2014;3(3):9-14. Russian.

8. Ovchinnikov VA, Uglyanitsa KN, Volkov VN. [Modern methods of radiation treatment of cancer patients]. Zhurnal GrGMU. GrGMU. 2010;(1):93-7. Russian.

9. Canti G, De Simone A, Korbelik M. Photodynamic therapy and the immune system in experimental oncology. J Photochem Photobiol. 2002;1:79-80.

10. Dolmans DE, Kadambi A, Hill GS, Flores KR, Gerber JN, Walker JP et al. Targeting tumor vasculature and cancer cells in orthotopic breast tumor by fractionated photosensitizer dosing photodynamic therapy. Cancer Res. 2002;62(15):4289-94.

11. Olivo M, Bhuvaneswari R, Swarnalatha SL, Dendukuri N, Soo-Ping Thong P. Targeted therapy of cancer using photodynamic therapy in combination with multi-faceted anti-tumor modalities. Pharmaucetical (Basel) 2010 May;3(5):1507-29.

12. Gollnick SO, Evans SS, Baumann H, Owczarczak B, Maier P, Vaughan L et al. Role of cytokines in photodynamic therapy - induced local and systemic inflammation. Br J Cancer. 2003;88(11):1772-9.

13. Dmitriyeva NV, Petukhova IN, Smolyanskaya AZ. [Infectious complications in the oncology clinic]. Prakticheskaya onkologia] 2001;1(5):18-20. Russian.

14. Jori G, Fabris C, Soncin M et al. Photodynamic therapy in the treatment of microbial infections: basic principles and perspective applications. Lasers Surg. Med. 2006;38:468-81.

15. Chandrasekaran B, Chettri R, Agrawal N, Sathyamoorthy C. Short-term multimodal phototherapy approach in a diabetic ulcer patient. Singapore Med J. 2012;53(6):122-4.

16. Stranadko YeF. Photodynamic therapy of purulent-inflammatory diseases of soft tissues. Fotobiologiya ta fotomeditsina. 2011;(2):14 9. Ukrainian.

17. Risovannaya OS. [Bacteriostatic therapy in the treatment of inflammatory diseases of periodontal tissues]. Lasernaya medicine. 2006;10(2):21-8. Russian.

18. Tolstykh PI., Koraboev UM., Shekhter AB. et al. [Experimental substantiation of the use of photodynamic therapy for the healing of purulent wounds]. Lasernaya meditsina. 2001;5(2):8-13. Russian.

19. Shishkina OE, Butakova LYu., Ivanchenko YuO., Antonov SS. [Microbiological substantiation of the effectiveness of photosensitizers in photodynamic therapy]. Lasernaya meditsina. 2013;17 (1):35-7. Russian.

20. Krasnovsky AA.[ Photodynamic action and singlet oxygen]. Biofisika. 2004;49(2):305-21.Russian.

21. Krasnoselsky NV, Simonova-Pushkar LI. Goni-Simeha AT., Sorokina IV, Miroshnichenko MS, V. Goleva NV. [Morphological characteristics and healing features of radiation ulcers of the skin infected with Pseudomonas aeruginosa]. Nauka i praktika. Mizhvidomchiy medichniy zhurnal. 2017;(1/2):64-8. Russian.

22. Skliar NI, Simonova-Pushkar LI, Sarkis-Ivanova VV, Hertman VZ. [Microbiological substantiation of the effectiveness of photodynamic therapy on the experimental model of infected skin ulcer]. Aktualni Problemy Suchasnoi Medytsyny. 2016;(4 Part 3):61-5. Ukrainian.

23. European convention for the protection of vertebrate animals used for experimental and other scientific purposes. Strasbourg: Council of Europe; 1986. 53 p.

24. Reznikov OH, Soloviov AI, Dobrelia nv, Stefanov OV. [Bioethical examination of preclinical and other scientific researches carried out on animals: a methodical recommendations]. Visnyk Farmakolohii ta Farmakopei. 2006;(7):47-60. Ukrainian.

25. Gubina-Vakulyk GI, Sorokina IV, Markovsky VD, et al., inventors; Kharkiv National Medical University, assignee. Ukrainian patent UA 46489. [The method of quantitative determination of antigen content in biological tissues]. 2009 Dec 25. Bulletin No. 4. Ukrainian.

26. Buhl A, Zofel P. SPSS, version 10. Enfuhrung in de modern Dateanalyse unter Windows. Munchen: Person Education Deutschland GmbH; 2001.

27. Ivanyuk EE, Nadezhdin SV, Pokrovskaya LA, Shupletsova VV, Khaziakhmatova OG, Yurova KA, et al. [Macrophage subsets and mesenchymal stem cells in regulation of bone tissue remodeling]. Tsitologiya. 2018;60(4):252-61. Russian.