The role of signaling molecules – factors of migration and adhesion of lymphocytes in the pathomorphosis of pulmonary tuberculoma
- Authors: Leontyeva D.O.1, Mironova E.S.1,2, Krylova Y.S.1,3, Kvetnoy I.M.1,4, Yablonsky P.K.1,4, Drobintseva A.O.1,5
-
Affiliations:
- FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation
- ANNO VO Research Center "St. Petersburg Institute of Bioregulation and Gerontology"
- Federal State Budgetary Educational Institution of Higher Education “First St. Petersburg StateMedical University named after. I.P. Pavlova" Ministry of Health of the Russian Federation
- FGBOU HE "St. Petersburg State University"
- FGBOU HE "St. Petersburg State Pediatric Medical University of the Ministry of Health of Russia"
- Issue: Vol 21, No 5 (2023)
- Pages: 41-46
- Section: Original research
- URL: https://journals.eco-vector.com/1728-2918/article/view/622786
- DOI: https://doi.org/10.29296/24999490-2023-05-06
- ID: 622786
Cite item
Open Access
Access granted
Abstract
Introduction. Tuberculosis is a socially significant disease, which is based on chronic granulomatous inflammation with the formation of fibrosis. The signaling molecules CD44 and ICAM-1 play an important role in the process of migration of immune cells from the bloodstream to the site of inflammation. CD44 is an integral cellular glycoprotein that plays an important role in cell-cell interactions, cell adhesion and migration. The strength of this interaction is ensured by the interaction of ICAM-1 with the LFA-1 antigen located on the surface of leukocytes. Thus, studying the expression levels of CD44 and ICAM-1 during the development of the tuberculosis process will expand our understanding of the involvement of immune cells in the pathomorphism of the disease.
The purpose of the study was to study the expression of markers of migration and adhesion of lymphocytes CD44 and ICAM-1 at various degrees of inflammatory activity in pulmonary tuberculoma.
Methods. The object of the study was tuberculoma, as a clinical form of pulmonary tuberculosis. Using immunohistochemistry and morphometry, the relative expression area of the CD44 and ICAM-1 proteins was determined depending on the degree of activity of the tuberculosis process.
Results. The level of relative expression of ICAM-1 in granulomas did not differ significantly from the degree of activity of the tuberculosis process. A decrease in the level of CD44 expression was observed with the 4th degree of activity of the tuberculosis process (widespread active inflammatory changes with beginning progression).
Conclusion. The expression level of ICAM-1 remained constant at all stages of tuberculoma pathomorphosis, while the CD44 expression level was significantly associated with the pathomorphosis of the disease, reaching minimum values at the 4th degree of activity of the pathological process. The data obtained indicate the constant involvement of ICAM-1 in the mechanisms of cell adhesion at all stages of granuloma formation. Low levels of CD44 expression in tuberculomas with grade 4 inflammatory changes reflect the cessation of migration of committed immune cells to the site of inflammation, thereby providing conditions for either stabilization of the pathological process by fibrosis of the granuloma, or, conversely, for the progression of the inflammatory process.
Keywords
Full Text
About the authors
Darya O. Leontyeva
FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation
Author for correspondence.
Email: info@spbniif.ru
ORCID iD: 0000-0001-6981-2531
Laboratory Researcher, Laboratory of Molecular Pathology, Department of Translational Biomedicine
Russian Federation, Ligovsky Ave., 2–4, St. Petersburg, 191036Ekaterina S. Mironova
FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; ANNO VO Research Center "St. Petersburg Institute of Bioregulation and Gerontology"
Email: katerina.mironova@gerontology.ru
ORCID iD: 0000-0001-8134-5104
Head of the Molecular Neuroimmunoendocrinology Laboratory, Department of Translational Biomedicine
Russian Federation, Ligovsky Ave., 2–4, St. Petersburg, 191036; Dynamo Ave., 3, St. Petersburg, 197110Yuliya S. Krylova
FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; Federal State Budgetary Educational Institution of Higher Education “First St. Petersburg StateMedical University named after. I.P. Pavlova" Ministry of Health of the Russian Federation
Email: emerald2008@mail.ru
ORCID iD: 0000-0002-8698-7904
Senior Researcher, Laboratory of Molecular Pathology, Department of Translational Biomedicine, St. Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of the Russian Federation, Ph.D
Russian Federation, Ligovsky Ave., 2–4, St. Petersburg, 191036; st. Leo Tolstoy, 6–8, St. Petersburg, 197022Igor M. Kvetnoy
FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; FGBOU HE "St. Petersburg State University"
Email: info@spbniif.ru
ORCID iD: 0000-0001-7302-5581
Head of Translational Biomedicine Department, St. Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of the Russian Federation, Professor, Doctor of Medical Sciences
Russian Federation, Ligovsky Ave., 2–4, St. Petersburg, 191036; Universitetskaya nab., 7/9, St. Petersburg, 199034Petr K. Yablonsky
FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; FGBOU HE "St. Petersburg State University"
Email: glhirurgb2@mail.ru
ORCID iD: 0000-0003-4385-9643
Director of the St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, Professor, Doctor of Medical Sciences
Russian Federation, Ligovsky Ave., 2–4, St. Petersburg, 191036; Universitetskaya nab., 7/9, St. Petersburg, 199034Anna O. Drobintseva
FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; FGBOU HE "St. Petersburg State Pediatric Medical University of the Ministry of Health of Russia"
Email: anna.drobintseva@gmail.com
ORCID iD: 0000-0002-6833-6243
Senior Researcher, Laboratory of Molecular Neuroimmunoendocrinology, Department of Translational Biomedicine, St. Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of the Russian Federation, Ph.D
Russian Federation, Ligovsky Ave., 2–4, St. Petersburg, 191036; st. Litovskaya, 2, St. Petersburg, 194100References
- Johnson P., Ruffell B. CD44 and its role in inflammation and inflammatory diseases. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy). 2009; 8 (3): 208–20.
- Racanelli A.C., Kikkers S.A., Choi A.M.K., Cloonan S.M. Autophagy and inflammation in chronic respiratory disease. Autophagy. 2018; 14 (2): 221–32.
- Апт А.С., Кондратьева Т.К. Туберкулез: патогенез, иммунный ответ и генетика хозяина. Молекулярная биология. 2008; 42 (5): 880–90. [Apt A.S., Kondrat'eva T.K. Tuberculosis: pathogenesis, immune response and host genetics. Molekulyarnaya biologiya. 2008; 42 (5): 880–90 (In Russian)].
- Moreira-Teixeira L., Tabone O., Graham C.M., Singhania A., Stavropoulos E., Redford P.S., O’Garra A. Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis. Nature immunology. 2020; 21 (4): 464–76.
- Saini V., Chinta K.C., Reddy V.P., Glasgow J.N., Stein A., Lamprecht D.A., Steyn A.J. Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis. Nature communications. 2020; 11 (1): 1–17.
- DeGrendele H.C., Kosfiszer M., Estess P., Siegelman M.H. CD44 activation and associated primary adhesion is inducible via T cell receptor stimulation. The Journal of Immunology. 1997; 159 (6): 2549–53.
- Patouraux S., Rousseau D., Bonnafous S., Lebeaupin C., Luci C., Canivet C.M., Gual P. CD44 is a key player in non-alcoholic steatohepatitis. J. of hepatology. 2017; 67 (2): 328–38.
- Huebener P., Abou-Khamis T., Zymek P., Bujak M., Ying X., Chatila K., Frangogiannis N.G. CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. The Journal of Immunology. 2008; 180 (4): 2625–33.
- Govindaraju P., Todd L., Shetye S., Monslow J., Puré E. CD44-dependent inflammation, fibrogenesis, and collagenolysis regulates extracellular matrix remodeling and tensile strength during cutaneous wound healing. Matrix Biology. 2019; 75: 314–30.
- Nandi A., Estess P., Siegelman M. Bimolecular complex between rolling and firm adhesion receptors required for cell arrest: CD44 association with VLA-4 in T cell extravasation. Immunity. 2004; 20 (4): 455–65.
- Khan A.I., Kerfoot S.M., Heit B., Liu L., Andonegui G., Ruffell B., Kubes P. Role of CD44 and hyaluronan in neutrophil recruitment. The Journal of Immunology. 2004; 173 (12): 7594–601.
- Johnson L.A., Jackson D.G. Hyaluronan and its receptors: key mediators of immune cell entry and trafficking in the lymphatic system. Cells. 2021; 10 (8): 2061.
- Johnson L.A., Lawrance W., Roshorn Y.M., Hanke T., Banerji S., Jackson D.G. The lymphatic vessel endothelial receptor LYVE-1 mediates dendritic cell entry to the afferent lymphatics via transmigratory cups that engage the leukocyte hyaluronan glycocalyx. Nat Immunol. 2017; 18: 762–70.
- Lawrance W., Banerji S., Day A.J., Bhattacharjee S., Jackson D.G. Binding of hyaluronan to the native lymphatic vessel endothelial receptor LYVE-1 is critically dependent on receptor clustering and hyaluronan organization. Journal of Biological Chemistry. 2016; 291 (15): 8014–30.
- Van Der Windt G.J., Hoogendijk A.J., De Vos A.F., Kerver M.E., Florquin S., Van Der Poll T. The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia. Laboratory Investigation. 2011; 91 (4): 588–97.
- Liang J., Jiang D., Griffith J., Yu S., Fan J., Zhao X., Bucala R., Noble P.W. CD44 is a negative regulator of acute pulmonary inflammation and lipopolysaccharide-TLR signaling in mouse macrophages. The Journal of Immunology. 2007; 178 (4): 2469–75.
- Teder P., Vandivier R.W., Jiang D., Liang J., Cohn L., Puré E., Henson P.M., Noble P.W. Resolution of lung inflammation by CD44. Science. 2002; 296 (5565): 155–8.
- Simmons D.L. The role of ICAM expression in immunity and disease. Cancer surveys. 1995; 24: 141–55.
- Windish H.P., Lin P.L., Mattila J.T., Green A.M., Onuoha E.O., Kane L.P., Flynn J.L. Aberrant TGF-β signaling reduces T regulatory cells in ICAM-1-deficient mice, increasing the inflammatory response to Mycobacterium tuberculosis. J. of leukocyte biology. 2009; 86 (3): 713–25.
- Aslam Z., Mumtaz M., Malkani N. Evaluation of serum circulating levels of ICAM-1 as tuberculosis risk-assessment factor in type 2 diabetes patients. Puerto Rico Health Sciences J. 2019; 38 (1): 22–6.
- Ариэль Б.М., Ковальский Г.Б., Блюм Н.М., Беллендир Э.Н. Туберкулез (рабочие стандарты патологоанатомического исследования). Библиотека патологоанатома. Науч.-практич. Журнал. СПб.: ГУЗ «ГПАБ», 2009; 101: 80. [Ariel' B.M., Koval'skij G.B., Blyum N.M., Bellendir E.N. Tuberculosis (Working Standards for Post-mortem Examination). Biblioteka patologoanatoma. Nauch.-praktich. Zhurnal. SPb.: GUZ «GPAB», 2009; 101: 80 (In Russian)].
Supplementary files
