The Role of Monocytes Cellular and Molecular Mechanisms in the Development of Systemic Immune Inflammation. Part 1

Introduction: the important role of monocytes /macrophages, as well as cytokines produced by them was determined in the pathogenesis of mental disorders, as a macrophage-T-lymphocyte theory of bipolar disorder, schizophrenia and depression. According to this theory, there is an increase in the number of active circulating monocytes, macrophages and T-cells in patients with mental disorders. These cells migrate to the CNS as a result of the blood-brain barrier breach, destabilize the brain and lead to worsening of mental disorders.

The aim of work: to review research data on the role of proinflammator monocytes in the development of immune inflammation in the pathogenesis of a number of systemic diseases and to examine the molecular mechanisms mediating the interaction of proinflammatory monocytes with other cells involved in immune inflammation.

Material and methods: keywords “proinflammatory monocyte CD16+”, “cytokines”, “molecules of cell adhesion”, “monocyte-platelet aggregates”, “microglia”, “psychiatriс disorders”, are used to search for data published over the past 20 years in domestic and foreign studies in PubMed and e-Library.

Conclusion: in the first part of the review, the research data concerning the studies of the functional characteristics of a monocytes subpopulation that express on their surface an increased level of CD16 receptors when activated were analyzed. Most of researchers associate the proinflammatory functions of monocytes with this subpopulation. Molecular mechanisms of monocytes activation, which include increased secretion of CD16 receptors, cytokines, chemokines and receptors for them involved in their interaction with vascular endothelial cells, with neurons in the CNS and also with platelets in the development of systemic inflammation, are considered. Analysis of these mechanisms allows us to better understand the immune aspects of inflammation in the brain mediated by the interaction of CD16+ monocytes with neuronal cells, which results in cognitive disorders in patients with mental disorders, as well as to identify related new approaches to the treatment of cognitive decline in these patients. Studies of the monocyte unit of immunity in patients with mental disorders will be covered in the second part of the review.

1. Smith R S. A comprehensive macrophage-Tlymphoc y te theor y of schizophrenia. Med. Hypotheses. 1992;39(3):248–57. DOI: 10.1016/0306-9877(92)90117-u

2. Nikkilä HV, Müller K, Ahokas A, Miettinen K, Rimón R, Andersson LC. Accumulation of macrophages in the CSF of schizophrenic patients during acute psychotic episodes. Am. J. Psychiatry 1999;156(11):1725–1729. https://DOI:10.1176/ajp.156.11.1725

3. Theodoropoulou S, Spanakos G, Baxevanis CN, Economou M, Gritzapis AD, Papamichail MP, Stefanis CN. Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients. Schizophr. Res. 2001;479(1):13–25. DOI: 10.1016/s0920-9964(00)00007-4

4. Takahashi V, Yu Z, Sakai Mai, Tomita H. Linking Activation of Microglia and Peripheral Monocytic Cells to the Pathophysiology of Psychiatr ic Disorders. Front. Cell. Neurosci. 2016;10:144. https://DOI:10.3389/fncel.2016.00144 eCollection 2016.

5. Nozadze DN, Rvacheva AV, Kaznacheeva EI, Sergienko IV. Monocytes in the development and destabilization of atherosclerotic plaques. Aterosklersisz and dislipidaemias. 2012;3(8):25–36. (In Russ.). https://cyberleninka.ru/article/n/monotsityv-razvitii-i-destabilizatsii-ateroskleroticheskoyblyashki/viewer

6. Auf fray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu. Rev. Immunol. 2009;27:669–692. https://DOI:10.1146/annurev.immunol.021908.132557

7. Yarilin AA. Immunology. Moscow: “GEOTAR-Media”. 2010:752. (In Russ.). http://www.geotar.ru/lots/Q0115299.html

8. Williams DW, Byrd D, Rubin LH, Anastos K , Morgello S., Berman JW. CCR2 on CD14(+)CD16(+) monocytes is a biomarker of HIV-associated neurocognitive disorders. Neurol. Neuroimmunol. Neuroinflamm. 2014;(1):36. https://DOI:10.1212/NXI.0000000000000036

9. Merino A, Buendia P, Martin-Malo A, Aljama P, Ramirez R. Carracedo J. Senescent CD14+CD16+ Monocytes Exhibit Proinflammatory and Proatherosclerotic Activity. J. Immunol. 2011;186(3):1809–1815. https://DOI.org/10.4049/jimmunol.1001866

10. Нansson GK, Edfeldt K. Toll to be paid at the gateway to the vessel wall. Arterioscler. Thromb Vasc Biol. 2005;(25):1085–87. https://DOI.org/10.1161/01.ATV.0000168894.43759.47

11. Freudenberg MA, Tchaptchet S, Keck S, Fejer G, Huber M, Schütze N, Beutler B, Galanos C. Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: benefits and hazards of LPS hypersensitivity. J. Immunobiology. 2008;213(3–4):193–203. https://DOI:10.1016/j.imbio.2007.11.008

12. Randhawa AK, Hawn TR. Toll-like receptors: their roles in bacterial recognition and respiratory infections. Expert Rev. Anti Infect. Ther. 2008;6(4):479–495. https://DOI:org10.1586/14787210.6.4.479

13. Strauss-Ayali D, Conrad SM, Mosser DM. Monocyte subpopulations and their differentiation patterns during infection. J. Leukoc. Biol. 2007;82(2):244–252. https://DOI:10.1189/jlb.0307191

14. Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J. Leukoc. Biol. 2007;81(3):584–592. https://DOI:org10.1189/jlb.0806510

15. Wong KL, Yeap WH, Tai JJ, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53(1–3):41–57. https://DOI:org/10.1007/s12026-012-8297-3

16. Zhu H, Ding Y, Zhang Y, Ding X, Zhao J, Ouyang W, Gong J, Zou Y, Liu X, Wu W. CTRP3 induces an intermediate switch of CD14++CD16+ monocyte subset with anti-inflammatory phenotype. Exp. Ther. Med. 2020;199(3):2243–2251. https://DOI:10.3892/etm.2020.8467 Epub 2020.01.23.

17. Krzyszkowski YuG, Grachev AN. Markers of monocytes and macrophages for the diagnosis of Immune pathology. Pathogenesis. 2012;10(1):14–19. (In Russ.). http://www.niiopp.ru/netcat_files/205/123/h_f1ffe2ac574b399597d3d0a07c53b735

18. Matveeva VG, Golovkin AS, Kudryavtsev IV, Grigoriev EV, Chernova MN. Dynamics of CD14+CD16+ monocyte subpopulations in complication-free systemic inflammatory response following coronary artery bypass graft surgery. Medical Immunology. 2012;14(4–5):391–398. (In Russ.). https://DOI.org/10.15789/1563-0625-2012-4-5-391-398

19. Barisione, Garibaldi S, Ghigliotti, Fabbi P, Altieri P, Casale MC, Spallarossa P, Bertero G, Balbi M, Corsiglia L, Brunelli C. CD14CD16 monocyte subset levels in heart failure patients. Dis. Markers. 2010;28(2):115–124. https://DOI:10.3233/DMA-2010-0691

20. Ancuta P, Liu KY, Misra V, Wacleche VS, Gosselin A, Zhou X, Gabuzda D. Transcriptional prof iling reveals developmental relationship and distinct biological functions of CD16+ and CD16-monocyte subsets. BMC Genomics. 2009;10:403–446. https://DOI:10.1186/1471-2164-10-403

21. Mosig S, Rennert K, Krause S, Kzhyshkowska J, Neunubel K, Heller R, Funke H. Different functions of monocyte subsets in familial hypercholesterolemia: potential function of CD14+ CD16+ monocytes in detoxif ication of oxidized LDL. FASEB J. 2009;23(3):866–74. https://DOI:10.1096/f j.08-118240

22. Kalashnikova AA, Voroshilova TM, Chinenova LV, Davydova NI, Kalinina NM. Monocyte subsets in healthy adults and sepsis patients. Medical Immunology. 2018;20(6):815–824. (In Russ.). https://DOI.org/10.15789/1563-0625-2018-6-815-824