1. Belarusian State Medical University, Minsk, Belarus 2. Republican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus 3. International Sakharov Environmental Institute of Belarusian State University, Minsk, Belarus
To date, there are no drugs that can prevent progressive destruction of lung tissue and small airway fibrosis in patients with chronic obstructive pulmonary disease (COPD). Therefore, molecular mechanisms of this disease are being studied. The aim of this study was to determine the chemokine receptor expression pattern of B-lymphocytes from peripheral blood and airways of patients with COPD. Peripheral blood was collected from 51 smokers with COPD, 21 healthy smokers, and 20 healthy non-smokers. Seven smokers with COPD and 7 healthy smokers were recruited to undergo bronchoscopy with bronchoalveolar lavage (BAL). The expression of chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5 on the surface of blood and BAL B-lymphocytes was determined by flow cytometry. It was found that the percentage of blood B-lymphocytes expressing chemokine receptors CCR5 and CXCR3 was higher in smokers with COPD compared with healthy smokers and healthy non-smokers. The percentage of CD27⁺ B-cells expressing CCR5 and CXCR3 receptors exceeded the proportion of CD27⁻ B-lymphocytes expressing these receptors in peripheral blood of patients with COPD and healthy controls. In smoking patients with COPD, the percentage of BAL B-cells expressing receptors CCR5 and CXCR3 was also increased compared with healthy smokers. There were no differences in the percentage of B-lymphocytes expressing receptors CXCR4, CXCR5, CCR6, and CCR7 in both peripheral blood and BAL between smokers with COPD and healthy smokers. A greater percentage of CD27⁻ B-lymphocytes than CD27⁺ B-cells expressed receptors CXCR4, CXCR5, CCR6, and CCR7 in the peripheral blood of smokers with COPD and healthy controls. The results of this study indicate a modification in the chemokine receptor profile of B-lymphocytes in COPD.
Kadushkin A.G. et al. Population rearrangement of B-lymphocytes expressing chemokine receptors in patients with chronic obstructive pulmonary disease // Biomeditsinskaya khimiya. - 2022. - V. 68. -N 2. - P. 134-143.
Kadushkin A.G. et al., "Population rearrangement of B-lymphocytes expressing chemokine receptors in patients with chronic obstructive pulmonary disease." Biomeditsinskaya khimiya 68.2 (2022): 134-143.
Kadushkin, A. G., Tahanovich, A. D., Movchan, L. V., Zafranskaya, M. M., Dziadzichkina, V. V., Shman, T. V. (2022). Population rearrangement of B-lymphocytes expressing chemokine receptors in patients with chronic obstructive pulmonary disease. Biomeditsinskaya khimiya, 68(2), 134-143.
Blanco I., Diego I., Bueno P., Casas-Maldonado F., Miravitlles M. (2019) Geographic distribution of COPD prevalence in the world displayed by Geographic Information System maps. Eur. Respir. J., 54(1), 1900610. CrossRef Scholar google search
Bystritskaya E.V., Bilichenko T.N. (2021) The morbidity, disability, and mortality associated with respiratory diseases in the Russian Federation (2015-2019) Pulmonologiya, 31(5), 551-561.] CrossRef Scholar google search
Polverino F., Seys L.J., Bracke K.R., Owen C.A. (2016) B cells in chronic obstructive pulmonary disease: moving to center stage. Am. J. Physiol. Lung Cell. Mol. Physiol., 311(4), L687-L695. CrossRef Scholar google search
Hogg J.C., Chu F., Utokaparch S., Woods R., Elliott W.M., Buzatu L., Cherniack R.M., Rogers R.M., Sciurba F.C., Coxson H.O., Paré P.D. (2004) The nature of small-airway obstruction in chronic obstructive pulmonary disease. New Engl. J. Med., 350(26), 2645-2453. CrossRef Scholar google search
Yadava K., Bollyky P., Lawson M.A. (2016) The formation and function of tertiary lymphoid follicles in chronic pulmonary inflammation. Immunology, 149(3), 262-269. CrossRef Scholar google search
Kato A., Hulse K.E., Tan B.K., Schleimer R.P. (2013) B-lymphocyte lineage cells and the respiratory system. J. Allergy Clin. Immunol., 131(4), 933-957. CrossRef Scholar google search
Hauser M.A., Legler D.F. (2016) Common and biased signaling pathways of the chemokine receptor CCR7 elicited by its ligands CCL19 and CCL21 in leukocytes. J. Leukocyte Biol., 99(6), 869-882. CrossRef Scholar google search
López-Giral S., Quintana N.E., Cabrerizo M., Alfonso-Pérez M., Sala-Valdés M., de Soria V.G., Fernández-Rañada J.M., Fernández-Ruiz E., Muñoz C. (2004) Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination. J. Leukocyte Biol., 76(2), 462-471. CrossRef Scholar google search
Litsiou E., Semitekolou M., Galani I.E., Morianos I., Tsoutsa A., Kara P., Rontogianni D., Bellenis I., Konstantinou M., Potaris K., Andreakos E., Sideras P., Zakynthinos S., Tsoumakidou M. (2013) CXCL13 production in B cells via Toll-like receptor/lymphotoxin receptor signaling is involved in lymphoid neogenesis in chronic obstructive pulmonary disease.Am. J. Respir. Crit. Care Med., 187, 1194-1202. CrossRef Scholar google search
Bracke K.R., Verhamme F.M., Seys L.J., Bantsimba-Malanda C., Cunoosamy D.M., Herbst R., Hammad H., Lambrecht B.N., Joos G.F., Brusselle G.G. (2013) Role of CXCL13 in cigarette smoke-induced lymphoid follicle formation and chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 188, 343-355. CrossRef Scholar google search
Förster R., Mattis A.E., Kremmer E.,Wolf E., Brem G., Lipp M. (1996) A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell, 87(6), 1037-1047. CrossRef Scholar google search
Müller G., Höpken U.E., Lipp M. (2003) The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity. Immunological Rev., 195, 117-135. CrossRef Scholar google search
Nie Y., Waite J., Brewer F., Sunshine M.J., Littman D.R., Zou Y.R. (2004) The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity. J. Exp. Med., 200(9), 1145-1156. CrossRef Scholar google search
Roos A.B., Sandén C., Mori M., Bjermer L., Stampfli M.R., Erjefält J.S. (2015) IL-17A is elevated in end-stage chronic obstructive pulmonary disease and contributes to cigarette smoke-induced lymphoid neogenesis. Am. J. Respir. Crit. Care Med., 191(11), 1232-1241. CrossRef Scholar google search
Kelsen S.G., Aksoy M.O., Georgy M., Hershman R., Ji R., Li X., Hurford M., Solomides C., Chatila W., Kim V. (2009) Lymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3. Am. J. Respir. Crit. Care Med., 179(9), 799-805. CrossRef Scholar google search
Bracke K.R., D'hulst A.I., Maes T., Demedts I.K., Moerloose K.B., Kuziel W.A., Joos G.F., Brusselle G.G. (2007) Cigarette smoke-induced pulmonary inflammation, but not airway remodelling, is attenuated in chemokine receptor 5-deficient mice. Clinical Experimental Allergy, 37(10), 1467-1479. CrossRef Scholar google search
Costa C., Traves S.L., Tudhope S.J., Fenwick P.S., Belchamber K.B., Russell R.E., Barnes P.J., Donnelly L.E. (2016) Enhanced monocyte migration to CXCR3 and CCR5 chemokines in COPD. Eur. Respir. J., 47(4), 1093-1102. CrossRef Scholar google search
Kadushkin A.G., Taganovich A.D., Arabey A.A., Shishlo L.M., Lyubetskaya A.P., Aleshkevich L.V. (2018) Sensitivity to glucocorticosteroids and heterogeneity of in vitro cell response in patients with chronic obstructive pulmonary disease. Pulmonologiya, 28(5), 558-566.] CrossRef Scholar google search
Arens R., Nolte M.A., Tesselaar K., Heemskerk B., Reedquist K.A., van Lier R.A., van Oers M.H. (2004) Signaling through CD70 regulates B cell activation and IgG production. J. Immunol., 173(6), 3901-3908. CrossRef Scholar google search
Sanz I., Wei C., Jenks S.A., Cashman K.S., Tipton C., Woodruff M.C., Hom J., Lee F.E. (2019) Challenges and opportunities for consistent classification of human B cell and plasma cell populations. Front. Immunol., 10, 2458. CrossRef Scholar google search
Sanz I., Wei C., Lee F.E., Anolik J. (2008) Phenotypic and functional heterogeneity of human memory B cells. Semin. Immunol., 20(1), 67-82. CrossRef Scholar google search
Brandsma C.A., Hylkema M.N., Geerlings M., van Geffen W.H., Postma D.S., Timens W., Kerstjens H.A. (2009) Increased levels of (class switched) memory B cells in peripheral blood of current smokers. Respir. Res., 10, 108. CrossRef Scholar google search
Tomankova T., Kriegova E., Liu M. (2015) Chemokine receptors and their therapeutic opportunities in diseased lung: far beyond leukocyte trafficking. Am. J. Physiol. Lung Cell. Mol. Physiol., 308(7), L603-L618. CrossRef Scholar google search
Henrot P., Prevel R., Berger P., Dupin I. (2019) Chemokines in COPD: from implication to therapeutic use. Int. J. Mol. Sci., 20(11), 2785. CrossRef Scholar google search
Kadushkin A.G., Shman T.V., Belevtsev M.V., Ibragimova Z.A., Taganovich A.D. (2013) Changes in T-lymphocyte population containing chemokine receptors in patients with chronic obstructive pulmonary disease. Pulmonologiya, 2, 41-45.] CrossRef Scholar google search
Ferrero M.R., Garcia C.C., Dutra de Almeida M., Torres Braz da Silva J., Bianchi Reis Insuela D., Teixeira Ferreira T.P., de Sá Coutinho D., Trindade de Azevedo C., Machado Rodrigues e Silva P., Martins M.A. (2021) CCR5 antagonist maraviroc inhibits acute exacerbation of lung inflammation triggered by influenza virus in cigarette smoke-exposed mice. Pharmaceuticals (Basel), 14(7), 620. CrossRef Scholar google search
Mcheik S., van Eeckhout N., de Poorter C., Galés C., Parmentier M., Springael J.Y. (2019) Coexpression of CCR7 and CXCR4 during B cell development controls CXCR4 responsiveness and bone marrow homing. Front. Immunol., 10, 2970. CrossRef Scholar google search