scholarly journals Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254886
Author(s):  
Takuya Ishikiriyama ◽  
Hiroyuki Nakashima ◽  
Kaori Endo-Umeda ◽  
Masahiro Nakashima ◽  
Seigo Ito ◽  
...  
Keyword(s):  
Kupffer Cells ◽  
Phagocytic Activity ◽  
Mononuclear Cells ◽  
Cholesterol Metabolism ◽  
Density Lipoprotein ◽  
Functional Responses ◽  
Tnf Α ◽  
Functional Features ◽  
Macrophage Populations

In the murine liver, there are two major macrophage populations, namely resident Kupffer cells (resKCs) with phagocytic activity and recruited macrophages (recMφs) with cytokine-producing capacity. This study was performed to clarify the functional differences between these two populations, focusing on their susceptibility to radiation and response to stimulation via liver X receptors (LXRs), which are implicated in cholesterol metabolism and immune regulation. Liver mononuclear cells (MNCs) were obtained from C57BL/6 (WT) mice with or without 2 Gy irradiation, and the phagocytic activity against Escherichia coli (E. coli) as well as TNF-α production were compared between the two macrophage populations. To assess LXR functions, phagocytosis, TNF-α production, and endocytosis of acetylated low-density lipoprotein (LDL) were compared after synthetic LXR ligand stimulation. Furthermore, LXRα/β knockout (KO) mice and LXRα KO mice were compared with WT mice. Irradiation decreased intracellular TNF-α production by recMφs but did not affect the phagocytic activity of resKCs. In vitro LXR stimulation enhanced E. coli phagocytosis by resKCs but decreased E. coli-stimulated TNF-α production by recMφs. Phagocytic activity and acetylated LDL endocytosis were decreased in both LXRα/β KO mice and LXRα KO mice, with serum TNF-α levels after E. coli injection in the former being higher than those in WT mice. In conclusion, resKCs and recMφs exhibited different functional features in response to radiation and LXR stimulation, highlighting their distinct roles liver immunity and lipid metabolism.

Comparative physiology of rodent pulmonary macrophages: in vitro functional responses

1988 ◽  
Vol 64 (5) ◽  
pp. 1953-1959 ◽  
Author(s):  
D. B. Warheit ◽  
M. A. Hartsky ◽  
M. S. Stefaniak
Keyword(s):  
Guinea Pig ◽  
Phagocytic Activity ◽  
Lung Cells ◽  
Comparative Physiology ◽  
Functional Responses ◽  
Inhaled Particles ◽  
Pulmonary Macrophages ◽  
The One ◽  
Formyl Peptides

Since toxicological testing of inhaled materials frequently requires utilization of several species, we have investigated pulmonary macrophage (PM) functional responses and compared the rat model with other rodents. Two strains of rats, three strains of mice, and one strain each of hamster and guinea pig were used in this study. The numbers of recovered cells by bronchoalveolar lavage generally correlated with animal body weight. The one exception was the Syrian Golden hamster from which increased numbers of macrophages were recovered. Cellular differential data obtained from lavaged cytocentrifuge preparations demonstrated that PM's account for greater than 97% of recoverable free lung cells for all species except the guinea pig, which contains a resident population of eosinophils. Cell morphology studies indicated that hamster PM exhibited the highest proportion of ruffled PM and demonstrated the highest phagocytic activity, whereas mouse PM phagocytic activity was significantly reduced compared with the other three species. In addition, chemotaxis studies showed that rat PM migrated best to zymosan-activated, complement-dependent chemoattractants, whereas hamster PM demonstrated an enhanced chemotactic response to N-formyl peptides. The results of these studies suggest that the rat may be the most efficient species for clearing inhaled particles, whereas hamsters and guinea pigs may best respond to bacteria.

scholarly journals Activated Macrophages of Monocytic Origin Predominantly Express Proinflammatory Cytokine Genes, Whereas Kupffer Cells Predominantly Express Anti-Inflammatory Cytokine Genes

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Anastasia Lokhonina ◽  
Andrey Elchaninov ◽  
Timur Fatkhudinov ◽  
Andrey Makarov ◽  
Irina Arutyunyan ◽  
...  
Keyword(s):  
Kupffer Cells ◽  
Differential Distribution ◽  
Cytokine Genes ◽  
Elevated Expression ◽  
The Central Nervous System ◽  
Macrophage Populations ◽  
Monocytic Lineage ◽  
Anti Inflammatory Cytokine

In the central nervous system and in the liver, the macrophage populations are represented exclusively by descendants of the hematopoietic progenitor cells of the yolk sac. The reasons for such differential distribution of macrophages are not fully understood. We found that, as can be judged by corresponding changes in the expression of CD86 and CD163 markers, the transient macrophages of monocytic lineage are more sensitive to activating stimuli. The two macrophage populations have distinct patterns of gene expression, which is particularly noticeable for M1- and M2-associated genes. For instance, Kupffer cells more readily develop and longer maintain the elevated expression levels of Il4, Il10, and Il13 upon the activation; by contrast, the macrophages of monocytic lineage express Il1b, Il12a, and Tnfα upon the activation. The obtained results allow us to conclude that the in vitro activated Kupffer cells of the liver are committed to M2 phenotype, whereas the in vitro activated monocyte-derived macrophages show a typical M1 behavior. These observations are likely to reflect the situation in the in vivo microenvironments.

Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice

2001 ◽  
Vol 281 (5) ◽  
pp. L1210-L1218 ◽  
Author(s):  
Robert Paine ◽  
Susan B. Morris ◽  
Hong Jin ◽  
Steven E. Wilcoxen ◽  
Susan M. Phare ◽  
...  
Keyword(s):  
Host Defense ◽  
Alveolar Macrophages ◽  
Phagocytic Activity ◽  
Wild Type ◽  
Specific Expression ◽  
Gm Csf ◽  
Functional Capabilities ◽  
Tnf Α

We hypothesized that pulmonary granulocyte-macrophage colony-stimulating factor (GM-CSF) is critically involved in determining the functional capabilities of alveolar macrophages (AM) for host defense. To test this hypothesis, cells were collected by lung lavage from GM-CSF mutant mice [GM(−/−)] and C57BL/6 wild-type mice. GM(−/−) mice yielded almost 4-fold more AM than wild-type mice. The percentage of cells positive for the β2-integrins CD11a and CD11c was reduced significantly in GM(−/−) AM compared with wild-type cells, whereas expression of CD11b was similar in the two groups. The phagocytic activity of GM(−/−) AM for FITC-labeled microspheres was impaired significantly compared with that of wild-type AM both in vitro and in vivo (after intratracheal inoculation with FITC-labeled beads). Stimulated secretion of tumor necrosis factor-α (TNF-α) and leukotrienes by AM from the GM(−/−) mice was greatly reduced compared with wild-type AM, whereas secretion of monocyte chemoattractant protein-1 was increased. Transgenic expression of GM-CSF exclusively in the lungs of GM(−/−) mice resulted in AM with normal or supranormal expression of CD11a and CD11c, phagocytic activity, and TNF-α secretion. Thus, in the absence of GM-CSF, AM functional capabilities for host defense were significantly impaired but were restored by lung-specific expression of GM-CSF.

Characterization of calves exhibiting a novel inheritable TNF-α hyperresponsiveness to endotoxin: associations with increased pathophysiological complications

2005 ◽  
Vol 98 (6) ◽  
pp. 2045-2055 ◽  
Author(s):  
T. H. Elsasser ◽  
J. W. Blum ◽  
S. Kahl
Keyword(s):  
Mononuclear Cells ◽  
Acute Phase Protein ◽  
Peripheral Blood Mononuclear ◽  
Lps Challenge ◽  
Genetic Potential ◽  
Tnf Α ◽  
Related Stress

A subpopulation of calves, herein termed “hyperresponders” (HPR), was identified and defined by the patterns of plasma TNF-α concentrations that developed following two challenges with endotoxin (LPS, 0.8 μg Escherichia coli 055:B5 LPS/kg0.75live body wt) separated by 5 days. The principle characteristic of HPR calves was a failure to develop tolerance to repeated LPS challenge that was evident in the magnitude of the TNF-α concentrations and prolonged severity of pathological sequellae. Whereas calves failing to develop LPS tolerance were identified on the basis of their excessive in vivo plasma TNF-α concentration responses, in vitro TNF-α responses of peripheral blood mononuclear cells isolated from each calf and challenged with LPS or PMA did not correlate or predict the magnitude of in vivo plasma TNF response of the calf. Intentional breeding to obtain calves from bulls and/or cows documented as HPR resulted in offspring displaying the HPR character when similar progeny calves were tested with LPS in vivo, with extensive controls in place to account for sources of variability in the general TNF-α response to LPS that might compromise interpretation of the data. Feed intake, clinical serology and hematology profiles, and acute-phase protein responses of HPR calves following LPS were significantly different from those of calves displaying tolerance. These results suggest that the pattern of plasma TNF-α changes that evolve from a low-level double LPS challenge effectively reveal the presence of a genetic potential for animals to display excessive or prolonged pathological response to LPS-related stress and compromised prognosis for recovery.

Ginseng Total Saponin Enhances the Phagocytic Capacity of Canine Peripheral Blood Phagocytes in Vitro

2008 ◽  
Vol 36 (02) ◽  
pp. 329-341 ◽  
Author(s):  
K. A. Kang ◽  
J. H. Kang ◽  
M. P. Yang
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Polymorphonuclear Cells ◽  
Phagocytic Capacity ◽  
Total Saponin ◽  
Tnf Α ◽  
Vitro Effect ◽  
Ginseng Total Saponin

The clinical and pharmacological activities of ginseng are known to modulate immune function, metabolic processes and neuro-endocrine system activities. Ginseng saponins are the principle active ingredients in the formation of immune stimulating complexes. The objective of this study was to evaluate the in vitro effect of ginseng total saponin (GTS) on the phagocytic capacity of canine peripheral blood phagocytes. GTS itself did not cause any direct effect on the phagocytic capacity of peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) but not peripheral blood monocytes. However, the phagocytic capacity of PMN and monocytes, but not PBMC, was enhanced by the culture supernatant from PBMC treated with GTS. The phagocytic capacity of PMN and monocytes was also increased by treatment with recombinant canine (rc) tumor necrosis factor (TNF)-α. The ability of the culture supernatant from GTS-treated PBMC to stimulate the phagocytic capacity of phagocytes was inhibited by addition of anti-rc TNF-α polyclonal antibody (pAb) prior to the culture. The amount of TNF-α in the culture supernatant from PBMC was shown to increase upon treatment of GTS as compared with that of vehicle-treated PBMC culture supernatant. These results suggest that GTS has an immunoenhancing effect on the phagocytic capacity of canine peripheral blood phagocytes, which is mainly mediated by TNF-α released from GTS-stimulated PBMC.

Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis

2003 ◽  
Vol 284 (2) ◽  
pp. R550-R557 ◽  
Author(s):  
Roy D. Goldfarb ◽  
Thomas S. Parker ◽  
Daniel M. Levine ◽  
Dana Glock ◽  
Imran Akhter ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Fibrin Clot ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Serum Lipoproteins ◽  
Treatment Groups ◽  
Tnf Α ◽  
Dose Dependent

Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-α, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.

Monocyte Derivatives Promote Angiogenesis and Myocyte Survival in a Model of Myocardial Infarction

2010 ◽  
Vol 19 (4) ◽  
pp. 369-386 ◽  
Author(s):  
M. Bouchentouf ◽  
P. Paradis ◽  
K. A. Forner ◽  
J. Cuerquis ◽  
M. N. Boivin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cell ◽  
Mononuclear Cells ◽  
Endothelial Cell Proliferation ◽  
Blood Monocytes ◽  
Vascular Networks ◽  
Peripheral Blood Mononuclear ◽  
Mature Endothelial Cell ◽  
Tnf Α

In this study, we have investigated the hypothesis that previously reported beneficial effect of peripheral blood mononuclear cells cultured under angiogenic conditions on cardiovascular function following ischemia is not limited to EPCs but also to monocytes contained therein. We first purified and analyzed the phenotype and secretome of human and murine blood monocytes cultured under angiogenic conditions (named MDs for monocyte derivatives) and tested their effect in a mouse model of myocardial infarction (MI). FACS analysis of MDs shows that these cells express mature endothelial cell markers and that their proliferative capacity is virtually absent, consistent with their end-differentiated monocytic ontogeny. MDs secreted significant levels of HGF, IGF-1, MCP-1, and sTNFR-1 relative to their monocyte precursors. MDs were unable to form vascular networks in vitro when cultured on matrix coated flasks. Treatment of murine HL-1 cardiomyocyte cell line with MD-conditioned medium reduced their death induced by TNF-α, staurosporine, and oxidative stress, and this effect was dependent upon MD-derived sTNFR-1, HGF, and IGF-1. We further demonstrate that MD secretome promoted endothelial cell proliferation and capacity to form vessels in vitro and this was dependent upon MD-derived MCP-1, HGF, and IGF-1. Echocardiography analysis showed that MD myocardial implantation improved left ventricle fractional shortening of mouse hearts following MI and was associated with reduced myocardial fibrosis and enhancement of angiogenesis. Transplanted MDs and their secretome participate in preserving functional myocardium after ischemic insult and attenuate pathological remodeling.

scholarly journals Diagnostic Implications of Antigen-Induced Gamma Interferon, Nitric Oxide, and Tumor Necrosis Factor Alpha Production by Peripheral Blood Mononuclear Cells from Mycobacterium bovis-Infected Cattle

2003 ◽  
Vol 10 (5) ◽  
pp. 960-966 ◽  
Author(s):  
W. R. Waters ◽  
M. V. Palmer ◽  
D. L. Whipple ◽  
M. P. Carlson ◽  
B. J. Nonnecke
Keyword(s):  
Bovine Tuberculosis ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Infected Cattle ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Bovine tuberculosis in the United States has proven costly to cattle producers as well as to government regulatory agencies. While in vivo responsiveness to mycobacterial antigens is the current standard for the diagnosis of tuberculosis, in vitro assays are gaining acceptance, especially as ancillary or complementary tests. To evaluate in vitro indices of cellular sensitization, antigen-induced gamma interferon (IFN-γ), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) responses by blood mononuclear cells from Mycobacterium bovis-infected cattle were quantified and compared. Using an aerosol model of infection, two doses of each of two strains of M. bovis (95-1315 and HC-2045T) were used to induce a range of IFN-γ, NO, and TNF-α responses. Infection-specific increases in NO, but not in IFN-γ or TNF-α, were detected in nonstimulated cultures at 48 h, a finding that is indicative of nonspecific activation and spontaneous release of NO. The infective dose of M. bovis organisms also influenced responses. At 34 days postinfection, IFN-γ, NO, and TNF-α responses in antigen-stimulated cells from cattle receiving 105 CFU of M. bovis organisms were greater than responses of cells from cattle infected with 103 CFU of M. bovis organisms. The NO response, but not the IFN-γ and TNF-α responses, was influenced by infective strains of M. bovis. The TNF-α, NO, and IFN-γ responses followed similar kinetics, with strong positive associations among the three readouts. Overall, these findings indicate that NO and TNF-α, like IFN-γ, may prove useful as indices for the diagnosis of bovine tuberculosis.

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