scholarly journals Functional and metabolic characteristics of peripheral blood mononuclear phagocytes in patients with different clinical courses of multiple sclerosis

2020 ◽  
Vol 11 (4) ◽  
pp. 494-500
Author(s):  
O. M. Koliada ◽  
N. I. Vdovichenko ◽  
T. I. Kolyada ◽  
O. P. Bilozorov

Functional and metabolic features of intact and stimulated mononuclear phagocytes were studied in patients with different clinical courses of multiple sclerosis, the study included 66 patients with relapsing-remitting and 32 patients with progressive course of multiple sclerosis. The state of the mononuclear phagocytes was characterized by expression of costimulatory molecules and direction of L-arginine metabolism. Relative quantities of CD80, CD86 and PD-L1 positive monocytes were determined with Phycoerytrin-labeled monoclonal antibodies in immunofluorescence test in peripheral blood and after culture in parallel series with addition of: (a) E.coli lipopolysaccharide (a stimulator of TLR4), (b) a single-stranded RNA – preparation ssRNA40/LyoVec (a stimulator of TLR7/8), (c) IL-4 (an anti-inflammatory interleukin). The formation of NO was determined by the amount of nitrite in the culture supernatants, arginase activity was determined in cell lysates of the monocyte fraction. We showed that functional and phenotypic characteristics of monocytes depend on the clinical course of multiple sclerosis. In patients with progressive course, the relative number of CD86+ cells was significantly higher and PD-L1+ cells significantly lower than in patients with relapsing-remitting course and healthy persons, in patients with relapsing-remitting course the number of PD-L1+ cells was increased. The number of CD80+ cells did not show any significant difference in the investigated groups of patients relative to the control group. In vitro stimulation of peripheral blood monocytes with TLR4/8 produced a significant increase in the number of CD86+ and decrease in the number of PD-L1+ cells in patients with the progressive course. In patients with the relapsing-remitting course LPS produced an increase in number of PD-L1+ cells. We did not find any difference in activity of the arginase pathway of L-arginine metabolism in the intact monocyte fraction of peripheral blood in patients with multiple sclerosis versus the control group, but stimulation with TLR4 agonist of mononuclear cells of patients with progressive course caused significant increased arginase activity versus baseline. At the same time, versus control cells arginase activity in patients with the progressive course decreased after LPS treatment, but trended to increase after TLR7/8 treatment. In patients with the relapsing-remitting course these changes had a similar direction but were less expressed. The results may be considered as an indication of the activation of peripheral blood monocytes and their polarization trend in the M1 direction in patients with the progressive course of multiple sclerosis, these changes could be considered as signs of violation of autoimmune regulatory mechanisms in multiple sclerosis.

2015 ◽  
Vol 44 (6) ◽  
pp. 590-601 ◽  
Author(s):  
Mehrdad Farrokhi ◽  
Masoud Etemadifar ◽  
Maryam Sadat Jafary Alavi ◽  
Sayyed Hamid Zarkesh-Esfahani ◽  
Mohaddeseh Behjati ◽  
...  

Author(s):  
Bahare Keshavarzi ◽  
Meraj Tabatabaei ◽  
Amir Hasan Zarnani ◽  
Fahime Ramezani Tehrani ◽  
Mahmood Bozorgmehr ◽  
...  

Background: The amniotic membrane plays an important role in maintaining a healthy pregnancy. The main population cells from amniotic membrane include human amnion epithelial cells (hAECs) which have been shown to possess immunomodulatory properties. Objective: The proximity of hAECs with monocyte leads to the generation of tollerogenic dendritic cells. Materials and Methods: hAECs were obtained from normal pregnancy. Peripheral blood monocytes were isolated by anti-CD14 MACS method. Co-cultures of monocytes and hAECs were established in Transwell chambers supplemented with granulocytemacrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in the absence and presence of lipopolysaccharide (LPS) to produce immature and mature DCs, respectively. Immunophenotyping of the obtained DCs was done through flow cytometry and the production of cytokines was measured by ELISA. Mixed leukocyte Reaction (MLR) was also performed for the functional assessment of DCs. Results: Immunophenotyping of [hAECs - Immature DC (iDC)] and [hAECs - iDC] + LPS cells revealed that the expression of CD1a, CD80, CD86, CD40, HLA-DR, and CD83 markers showed no significant difference as compared with the control group (iDCs and mDCs alone). In the [hAECs-iDCs] + LPS cells, the percentage of CD14 cells at the ratio of 1:2.5 showed significant differences compared to the control group. The production of IL-10 and IL-12 showed no significant difference in any of the cultures as compared to the control groups. Also, co-cultured DCs did not inhibit proliferation of lymphocyte. Conclusion: Our findings show that factors secreted from cultured hAECs are unable to generate of tollerogenic dendritic cells. To achieve a better understanding of other mechanisms more investigations are needed. Key words: Amniotic membrane, Dendritic cells, Human placenta, Immunomodulation, Monocyte.


1999 ◽  
Vol 276 (1) ◽  
pp. L164-L174 ◽  
Author(s):  
Michael James Tino ◽  
Jo Rae Wright

Surfactant protein (SP) A and SP-D are the pulmonary members of the collectin family, structurally related proteins involved in innate immune responses. Here, we have examined the abilities of SP-A, SP-D, mannose-binding protein (MBP), and the complement component C1q to stimulate actin-based cellular functions in rat alveolar macrophages and peripheral blood monocytes. Our goal in this study was to examine the cell specificity of the effects of the collectins to understand further the mechanisms by which SP-A and SP-D stimulate alveolar macrophages. We found that SP-A and SP-D have lung cell-specific effects at physiologically relevant concentrations; they stimulate directional actin polymerization and chemotaxis in alveolar macrophages but not in monocytes. Although C1q and MBP weakly stimulate the rearrangement of actin in both cell types, C1q is chemotactic only for peripheral blood monocytes and MBP does not stimulate chemotaxis of either cell type. Neither C1q nor MBP stimulates actin polymerization in alveolar macrophages. These results support the hypothesis that alveolar macrophages express receptors specific for the pulmonary collectins SP-A and SP-D and provide insight into the potential roles of collectins in the recruitment and maturation of mononuclear phagocytes in the lung.


1970 ◽  
Vol 131 (3) ◽  
pp. 429-442 ◽  
Author(s):  
Jan Thompson ◽  
Ralph van Furth

The effect of glucocorticosteroids on the kinetics of mononuclear phagocytes, i.e., peripheral blood monocytes and peritoneal macrophages, was studied in normal mice, as well as in mice in which an inflammatory reaction was evoked in the peritoneal cavity. The administration of glucocorticosteroids resulted in a rapid decrease (within 3–6 hr) in the number of circulating monocytes, the duration being dependent on the nature and dose of the compound. The water-soluble dexamethasone sodium phosphate is only briefly active (less than 12 hr), but hydrocortisone acetate, which forms a subcutaneous depot, reduced the number of monocytes for more than 2 wk. In normal mice, hydrocortisone did not affect the number of macrophages already present in the peritoneal cavity, but the transit of mononuclear phagocytes from the circulation into the peritoneal cavity was arrested. During an inflammatory response in the peritoneal cavity, hydrocortisone suppresses both the increase in the number of monocytes in the peripheral blood and the increase in the number of peritoneal macrophages. This reduction of the inflammatory exudate appeared to be due to a diminished influx of mononuclear phagocytes from the peripheral blood. No lytic action of glucocorticosteroids on the mononuclear phagocytes could be demonstrated.


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