scholarly journals Immune Aging and How It Works for Inflammation and Fibrosis

2022 ◽  
Vol 12 ◽  
Author(s):  
Hiroshi Nishiura ◽  
Mai Imasaka ◽  
Koji Yamanegi ◽  
Jiro Fujimoto ◽  
Masaki Ohmuraya

Almost all mature cells that undergo apoptosis in an age-dependent or an accidental manner are completely recovered in tissue-specific microenvironments without any physiological changes. After peripheral blood leukocytes are released into the local region, fibroblast cells and new blood vessels commonly proliferate during wound healing. Inducible repair tools mainly supplied from blood vessels are cleared by peripheral blood phagocytic macrophages. Finally, hematopoietic stem cell (HSC)-derived precursor cells migrate from bone marrow (BM) to the microenvironment to rebuild damaged tissues (the mature immune system). In contrast to the mature immune system, the effects of aging on HSCs (long-term HSCs) and peripheral blood lymphocytes (long-term PBLs) are not clearly understood in the BM and thymus niches with tissue-specific microenvironments with some physiological changes (the aged BM niche) for incomplete rebuilding of damaged tissues (the aged immune system). In this review, the roles of the aged immune system in both a delay of acute inflammation and the development of chronic inflammation or fibrosis are discussed.

1995 ◽  
Vol 181 (1) ◽  
pp. 369-374 ◽  
Author(s):  
K J Grzegorzewski ◽  
K L Komschlies ◽  
S E Jacobsen ◽  
F W Ruscetti ◽  
J R Keller ◽  
...  

Administration of recombinant human interleukin 7 (rh)IL-7 to mice has been reported by our group to increase the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakarocyte macrophage) from the bone marrow to peripheral organs (blood, spleen[s], and liver). We now report that IL-7 also stimulates a sixfold increase in the number of more primitive CFU-S day 8 (CFU-S8) and day 12 (CFU-S12) in the peripheral blood leukocytes (PBL) of mice treated with rhIL-7 for 7 d. Moreover, > 90% of lethally irradiated recipient mice that received PBL from rhIL-7-treated donor mice have survived for > 6 mo whereas none of the recipient mice that received an equal number of PBL from diluent-treated donors survived. Flow cytometry analysis at 3 and 6 mo after transplantation revealed complete trilineage (T, B, and myelomonocytic cell) repopulation of bone marrow, thymus, and spleen by blood-borne stem/progenitor cells obtained from rhIL-7-treated donor mice. Thus, IL-7 may prove valuable for mobilizing pluripotent stem cells with long-term repopulating activity from the bone marrow to the peripheral blood for the purpose of gene modification and/or autologous or allogeneic stem cell transplantation.


2019 ◽  
Vol 98 (10) ◽  
pp. 1091-1095
Author(s):  
Elena V. Boklazhenko ◽  
G. M. Bodienkova

Introduction. Based on the current understanding of the progression of professional chronic mercury intoxication, it is extremely important to study the regulatory activity of immunocompetent cells after the cessation contact with mercury to develop effective therapeutic measures. The purpose of the study was to study the population and subpopulation spectrum of peripheral blood lymphocytes and their cooperation in patients with chronic mercury intoxication in a distant postexposure period. Material and methods. Phenotyping of lymphocytes in the blood of the subjects was carried out by the method of indirect immunofluorescence using monoclonal antibodies to the molecules CD3+, CD4+, CD8+, CD9+, CD16+, CD20+, CD21+, CD23+, CD25+, CD95+. Results. In patients with chronic mercury intoxication in the long-term postexposure period, there were revealed features of the immune system functioning, indicating hyperactivation of both T- and B-components of the immune system. An increase in the total population of T-lymphocytes was established due to an increase in cells with receptors CD4+ (T-lymphocyte-helper cells) and CD16+ (killer cells), as well as an increase in the number of mature B-lymphocytes (CD20+) and pre-B-immature-lymphocytes (CD9+). Changes in the system of lymphocyte apoptosis, characterized by an increase in the number of cells expressing receptors for readiness for Fas-dependent apoptosis (CD95+), have been recorded. The established relationships between populations and subpopulations of lymphocytes indicate their importance in the implementation of the immune response, high activity and contingency between the components of the immune system in persons with chronic mercury intoxication after the termination of contact with the toxicant. Conclusion. The results obtained are the basis for long-term monitoring of the health status and improvement of the tactics of treating patients with neurointoxication with mercury in the postexposure period.


2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Tom Seijkens ◽  
Marten A. Hoeksema ◽  
Linda Beckers ◽  
Svenja Meiler ◽  
Esther Smeets ◽  
...  

During homeostasis hematopoietic stem and progenitor stem cells (HSPCs) give rise to lymphoid and myeloid cells as well as platelets and erythrocytes. However, during chronic inflammatory conditions hematopoiesis is often skewed towards the myeloid lineage, thereby potentially aggravating the ongoing inflammation. Here we investigated the effects of hypercholesterolemia on HSPCs during atherogenesis. Hypercholesterolemia increased HSPCs, defined as Lin - Sca1 + cKit - , in the bone marrow (BM) of LDLr -/- mice by 253.1%. The number of granulocyte-monocyte progenitors, BM granulocytes and BM monocytes was increased by 18.1%, 34.8% and 13.2%, respectively. In accordance, the myeloid colony forming potential of hypercholesterolemic BM was increased by 25.8%. Peripheral blood monocytes and granulocytes were increased by 203.0% and 161.1%, respectively. Competitive bone marrow transplantations (cBMT) in which we compared the effects of normo- vs. hypercholesterolemia primed HSPCs confirmed that the hypercholesterolemic microenvironment activates HSPCs, as reflected by a 26.5% increased reconstitution of peripheral blood leukocytes 10 weeks after the cBMT. Moreover, hypercholesterolemia-primed, and not normocholesterolemia-primed HSPCs acquired an enhanced propensity to generate myeloid cells, especially granulocytes and Ly6C high monocytes, even under long-term normocholesterolemic conditions in the recipient animals. cBMT demonstrated that hypercholesterolemia-induced activation of HSPCs increased atherosclerosis in LDLr -/- mice by 122.1% and increased CD45.1 + plaque leukocytes by 76.1%. Macrophages differentiated from hypercholesterolemia-primed BM produced increased levels of TNFα (+21.3%), IL6 (+17.4%) and MCP1 (+10.5%) compared to their normocholesterolemic counterparts, demonstrating that hypercholesterolemia-induced priming of HSPCs increased the inflammatory phenotype of their mature offspring. These results demonstrate that hypercholesterolemia-induced priming of HSPCs aggravates atherosclerosis by skewing hematopoiesis towards the pro-inflammatory myeloid lineages. Inhibition of this pro-inflammatory differentiation pathway on HSPC level has the potential to reduce atherosclerosis.


2020 ◽  
Vol 33 (11) ◽  
pp. 1047-1047
Author(s):  
Wan-yue Liu ◽  
Yi Sun ◽  
Shu-na Huang ◽  
Yu-zhen Lin ◽  
Hong-yan Guo ◽  
...  

Abstract Background To investigate the main environmental factors of hypertension and the relationship between hypertension and circular RNAs in peripheral blood lymphocytes. Methods This was a case–control study. A total of 681 hypertension patients and 485 subjects without hypertension were recruited between April 2017 and October 2018. All participations completed the questionnaire investigation, physical examination, and laboratory detection. Quantitative real-time polymerase chain reaction was used to analyze circRNAs (hsa_circ_0001946 and hsa_circ_0125589) in peripheral blood leukocytes in 84 hypertensives and 84 controls. Multivariate logistic regression and crossover analysis were used to analyze the interaction and association between environmental factors and circRNAs in hypertension. Results After adjusted by gender, age and marital status, overweight/obesity (odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.24–2.22), abdominal obesity (OR = 2.17, 95% CI 1.54–3.04), anxiety (OR = 2.15, 95% CI 1.41–3.28), family history of hypertension (OR = 4.26, 95% CI 3.18–5.70), and higher levels of hsa_circ_0001946 (OR = 4.13, 95% CI 1.85–9.21) were risk factors for hypertension, while levels of hsa_circ_0125589 were not associated with hypertension. Crossover analysis showed that the risk of hypertension was 13.12 times higher (95% CI 3.89–44.23) in overweight subjects with high hsa_circ_0001946 levels compared with normal weight subjects with low hsa_circ_0001946 levels. Further, the risk of hypertension was 17.78 times higher (95% CI 1.88–168.61) in subjects with anxiety and high hsa_circ_0001946 levels. Conclusions Hypertension is the result of both environmental factors and genetic factors. Higher hsa_circ_0001946 levels, overweight and anxiety may increase the risk of hypertension, while hsa_circ_0125589 levels are not related to hypertension.


2013 ◽  
Vol 11 (1) ◽  
pp. 625-633 ◽  
Author(s):  
Philippe Brunet de la Grange ◽  
Marija Vlaski ◽  
Pascale Duchez ◽  
Jean Chevaleyre ◽  
Veronique Lapostolle ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wagner de Fátima Pereira ◽  
Gustavo Eustáquio Alvim Brito-Melo ◽  
Cláudia Martins Carneiro ◽  
Dirceu de Sousa Melo ◽  
Karine Beatriz Costa ◽  
...  

The present study aimed to evaluate the expression of CD80 and CD18 in subpopulations of peripheral blood leukocytes and oxidative kidney damage in rats with nephrotic syndrome (NS) induced by doxorubicin (Dox) in comparison to control animals at different time points. Male adult Wistar rats were submitted to 24-hour urine and blood collection for biochemical and immunological analysis at 7, 14, 21, and 28 days after Dox injection. After euthanasia, the kidneys were removed for histological analysis and the evaluation of oxidative stress. The phenotypic characterization of leukocytes was performed using flow cytometry. Dox-injected animals exhibited increased CD18 expression in cytotoxic T lymphocytes, NK cells, and monocytes and high CD80 expression in monocytes. Kidney oxidative damage was positively correlated with CD80 expression in monocytes and serum levels of creatinine. These results suggest that phagocytic and cytotoxic cells are preferentially recruited to the tissue injury site, which may contribute to kidney dysfunction in this animal model of NS. The blockade of integrin and costimulatory molecules may provide new therapeutic opportunities for NS.


Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 271-275
Author(s):  
SD Rowley ◽  
M Zuehlsdorf ◽  
HG Braine ◽  
OM Colvin ◽  
J Davis ◽  
...  

Autologous bone marrow transplants (BMTs) can repopulate the hematologic system of patients treated with marrow-ablative chemotherapy and/or radiotherapy. However, treatment of the bone marrow graft to eliminate residual tumor cells prior to reinfusion can delay the return of peripheral blood elements, presumably from damage to or loss of hematopoietic stem cells responsible for hematologic recovery. To develop a model predictive of hematologic recovery, we studied the progenitor cell contents of 4-hydroperoxycyclophosphamide (100 micrograms/mL)-purged bone marrow grafts of 40 consecutive patients undergoing autologous BMT at this center. Granulocyte-macrophage colonies (CFU-GM) were grown from all grafts after treatment with this chemotherapeutic agent, but erythroid (BFU-E) and mixed (CFU-GEMM) colonies were grown from only 44% and 33% of the grafts respectively. The recovery of CFU-GM after purging ranged from 0.07% to 23%. The logarithm of CFU-GM content of the treated grafts was linearly correlated with the time to recovery of peripheral blood leukocytes (r = -0.80), neutrophils (r = -0.79), reticulocytes (r = -0.60), and platelets (r = -0.66). The CFU-GM content of purged autologous bone marrow grafts may reflect the hematopoietic stem cell content of the grafts and thus predict the rate of hematologic recovery in patients undergoing autologous BMT.


PEDIATRICS ◽  
1979 ◽  
Vol 64 (4) ◽  
pp. 515-519
Author(s):  
E. Fred Saunders ◽  
Grant Gall ◽  
Melvin H. Freedman

Granulopoiesis was studied in 10 children with Shwachman's syndrome (chronic neutropenia and exocrine pancreatic insufficiency). Marrow proliferative activity assessed by determination of mitotic indices and tritiated thymidine uptake into granulocytic cells was normal. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system demonstrated normal CFU-C numbers in four patients and reduced numbers in five. The granulocyte colonies formed were indistinguishable from normal colonies morphologically. Production of colony-stimulating activity (CSA) from patients' peripheral blood leukocytes appeared normal when tested on control marrow. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow, and co-culture of patients' peripheral blood lymphocytes with control marrow did not inhibit CFU-C growth. We conclude that in Shwachman's syndrome committed granulocytic stem cells are present, and the numbers detected in vitro vary widely as does the clinical neutropenia. The proliferative activity of recognizable granulocytic cells is normal and neither a deficiency of humoral stimulators nor the presence of serum or cellular inhibitors of granulopoiesis can be demonstrated.


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