scholarly journals Changes in Phenotypic Patterns of Blood Monocytes After Kidney Transplantation and During Acute Rejection

2021 ◽  
pp. 709-721
Author(s):  
V ŠVACHOVÁ ◽  
L KRUPIČKOVÁ ◽  
M NOVOTNÝ ◽  
M FIALOVÁ ◽  
K MEZEROVÁ ◽  
...  

Peripheral blood monocytes, which serve as precursors for tissue macrophages and dendritic cells (DC), play a key role in the immune response to kidney allograft, reparation processes and homeostasis regulation. In this prospective study, we used multicolor flow cytometry to monitor the phenotypic patterns of peripheral monocytes in subjects with uncomplicated outcomes and those with acute rejection. We found a reciprocal increase in the proportion of “classical monocytes” (CD14+CD16-) along with a decline in pro-inflammatory “intermediary” (CD14+CD16+) and “non-classical” (CD14lowCD16+) monocytes in subjects with normal outcomes. In subjects with acute rejection, we observed no reduction in “intermediary” monocytes and no increase in “classical” monocytes. Patients with uncomplicated outcomes exhibited downregulated HLA-DR in all three monocyte subpopulations. However, non-classical monocytes were unaffected in subjects with acute rejection. Expression of CD47 was downregulated after transplantation, while patients with antibody-mediated rejection and donor-specific antibodies showed higher pre-transplant values. In monocytes isolated at the time of biopsy, CD47 expression was higher in individuals with acute rejection compared to patients with normal outcomes one year post-transplant. Expression of CD209 (DC-SIGN) and the proportion of CD163+CD206+ subpopulations were upregulated during the first week after kidney transplantation. CD209 was also upregulated in samples taken on the day of biopsy confirming acute rejection. Our data demonstrate that kidney allograft transplantation is associated with phenotypic changes in peripheral blood monocytes during acute rejection.

2021 ◽  
pp. 1-9
Author(s):  
Laura P. Hughes ◽  
Marilia M.M. Pereira ◽  
Deborah A. Hammond ◽  
John B. Kwok ◽  
Glenda M. Halliday ◽  
...  

Background: Reduced activity of lysosomal glucocerebrosidase is found in brain tissue from Parkinson’s disease patients. Glucocerebrosidase is also highly expressed in peripheral blood monocytes where its activity is decreased in Parkinson’s disease patients, even in the absence of GBA mutation. Objective: To measure glucocerebrosidase activity in cryopreserved peripheral blood monocytes from 30 Parkinson’s disease patients and 30 matched controls and identify any clinical correlation with disease severity. Methods: Flow cytometry was used to measure lysosomal glucocerebrosidase activity in total, classical, intermediate, and non-classical monocytes. All participants underwent neurological examination and motor severity was assessed by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale. Results: Glucocerebrosidase activity was significantly reduced in the total and classical monocyte populations from the Parkinson’s disease patients compared to controls. GCase activity in classical monocytes was inversely correlated to motor symptom severity. Conclusion: Significant differences in monocyte glucocerebrosidase activity can be detected in Parkinson’s disease patients using cryopreserved mononuclear cells and monocyte GCase activity correlated with motor features of disease. Being able to use cryopreserved cells will facilitate the larger multi-site trials needed to validate monocyte GCase activity as a Parkinson’s disease biomarker.


1996 ◽  
Vol 5 (5) ◽  
pp. 362-369
Author(s):  
W. A. T. Slieker ◽  
P. Th. W. van Hal ◽  
J. M. Wijkhuijs ◽  
J. P. M. Hopstaken-Broos ◽  
J. A. Noordhoek ◽  
...  

At present, inhaled glucocorticoids are widely accepted as the therapy of choice in chronic asthma. Treatment with inhaled glucocorticoids significantly suppresses local airway inflammation in asthmatics, but may also have systemic effects, e.g. a reduction of the number of circulating hypodense eosinophils or a down-modulation of HLA-DR antigen (Ag) expression by T lymphocytes in peripheral blood. However, the effect of long-term therapy with inhaled glucocorticoids on peripheral blood monocytes (PBM), which are the precursors of the most numerous cell type in the lung, the alveolar macrophage, have not yet been evaluated. We therefore investigated the expression of various cell surface Ag on PBM from non-smoking patients with allergic asthma who were treated for 2.5 years with a β2-receptor agonist plus either an inhaled glucocorticoid (beclomethasone dipropionate, BDP) (n= 4) or an anticholinergic or placebo (n= 8). We compared the results with healthy volunteers (n= 7). Long-term treatment of allergic asthmatics with inhaled BDP, but not anticholinergic or placebo therapy, was associated with a significantly lower CDllb Ag expression (p< 0.04) and higher expression of CD13, CD14 and CD18 Ag (p< 0.05,p< 0.02 andp< 0.04, respectively) when compared with the healthy control subjects (n= 7). Most interestingly, PBM of asthmatics treated with inhaled BDP expressed an almost two-fold higher level of CD14 Ag on their cell surface than PBM of patients treated with anticholinergic or placebo (p< 0.03). No significant differences in the expression of CD16, CD23, CD25, CD32 and CD64 Ag or HLA-DR were observed between PBM from the different patient groups or healthy controls. Taken together, this study shows that long-term local therapy with inhaled BDP coincides with an altered expression of at least one cell surface Ag on PBM from allergic asthmatics.


1995 ◽  
Vol 13 (9) ◽  
pp. 2324-2329 ◽  
Author(s):  
M Wiesenfeld ◽  
M J O'Connell ◽  
H S Wieand ◽  
N J Gonchoroff ◽  
J H Donohue ◽  
...  

PURPOSE The primary goal of this study was to assess the effectiveness of interferon gamma (IFN-gamma) to prevent tumor relapse following potentially curative surgery in patients with high-risk colon cancer. A secondary goal was to determine the effect of IFN-gamma on immune function and to correlate alterations in immune parameters with survival. PATIENTS AND METHODS Three to 4 weeks after undergoing resection of all known malignant disease, 99 patients with stage II, III, or IV colon cancer were randomly assigned to receive IFN-gamma 0.2 mg total dose by subcutaneous injection daily for 6 months or observation. Serial assessment of human leukocyte antigen (HLA)-DR expression and Fc receptors on peripheral-blood monocytes was conducted in 24 patients who received IFN-gamma and 27 control patients. RESULTS With a median follow-up duration of 59 months in patients still alive, there was evidence of a detrimental effect on time to relapse (P = .03) among patients who received IFN-gamma. There was no significant difference in patient survival (P = .12). This study has sufficient power to rule out a 25% reduction in death rate for patients who received IFN-gamma (P < .05). Significant enhancement of immune function was observed in patients treated with IFN-gamma as measured by HLA-DR expression (P < .01) and Fc receptors (P < .001) on peripheral-blood monocytes. CONCLUSION This study effectively rules out any clinically meaningful benefit for IFN-gamma as surgical adjuvant treatment for patients with high-risk colon cancer. Although significant enhancement of nonspecific immune function was seen with this dosage administration schedule of IFN-gamma, this was not associated with any demonstrable antitumor effect.


1991 ◽  
Vol 161 (6) ◽  
pp. 639-645 ◽  
Author(s):  
William G. Cheadle ◽  
Michael J. Hershman ◽  
Samuel R. Wellhausen ◽  
Hiram C. Polk

1999 ◽  
Vol 1 (3) ◽  
pp. 146-152 ◽  
Author(s):  
J.W. Haveman ◽  
A.P. Van Den Berg ◽  
J.M.M. Van Den Berk ◽  
G. Mesander ◽  
M.J.H. Slooff ◽  
...  

2020 ◽  
Vol 22 (2) ◽  
pp. 347-356
Author(s):  
A. A. Savchenko ◽  
A. G. Borisov ◽  
I. V. Kudryavtsev ◽  
A. V. Moshev

The aim of this work was to reveal the interrelations between the number of T regulatory cells (Tregs) in patients with kidney cancer (KC) and phenotype of peripheral blood monocytes and their capacities to produce ROS. Patients with KC (T3N0M0, clear cell type) were examined prior to surgical treatment. Tregs phenotype and blood monocytes were identified by flow cytometry. ROS production of purified monocytes was carried out through the determination of lucigenin- and luminol-dependent spontaneous and zymosan-induced chemiluminescence activity. It has been found that the relative number of Tregs within total lymphocyte subset in KC patients was increased if compared to control values (in KC patients — Me = 6.3%). Then the patients were divided into two groups according to the median of Tregs number (less and more than 6.3%). The most pronounced changes in the phenotype of monocytes and their chemiluminescent activity were found in KC patients with the Tregs count of less than 6.3%. Our findings suggest that low frequency of Tregs in the periphery was associated with increased relative numbers of “intermediate” and “non-classical” (“pro-inflammatory”) monocytes as it was shown on the samples from patients with KC with a low level of Tregs. According to our data, both groups of KC patients had low levels of HLA-DR expression when comparing to control group. Furthermore, both groups of patients had decreased rates of HLA-DR and CD64 co-expressing cells. Changes in the phenotype of monocytes in patients with KC were closely linked with imbalance in ROS production. Thus, the monocytes spontaneous superoxide radical (primary ROS) synthesis in KC patients with a low Treg numbers were characterized by redused NADPH-oxidase activation time and increased level of its activity if compared to patients with a high Treg rates in peripheral blood. Next, the activation index for lucigenin-dependent chemiluminescence in KC patients was reduced, as well as it was independent of circulating Tregs rates and was determined apparently by the insufficiency of metabolic reserves. Similarly, spontaneous secondary ROS production by the monocytes in KC patients was lower then in healthy controls and was also independent of circulating Tregs rates. Finally, the induced secondary ROS synthesis and activation index for their synthesis in monocytes were reduced only in patients with KC with a low number of Tregs in the blood. In general, the characteristics of the chemiluminescent reaction of monocytes in patients with KC determined the imbalance in peripheral blood monocytes primary and secondary ROS production. Monocytes in patients with KC with a low number of Tregs in the blood were characterized by more pro-inflammatory activity due to the rapid activation and intensity of the synthesis of primary ROS.


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