scholarly journals ENZYMES OF TUBERCULOUS TISSUE

1908 ◽  
Vol 10 (5) ◽  
pp. 645-665 ◽  
Author(s):  
Eugene L. Opie ◽  
Bertha I. Barker
Keyword(s):  
Mononuclear Cells ◽  
Mononuclear Phagocytes ◽  
Normal Blood ◽  
Tubercle Bacillus ◽  
Epithelioid Cells ◽  
Lymphatic Gland ◽  
Inflammatory Exudate ◽  
Tuberculous Lesion ◽  
By Products ◽  
Pleural Exudate

Epithelioid cells which form the chief element of tuberculous tissue contain an enzyme which causes active digestion of proteid in an approximately neutral or in a weakly acid medium, but is inactive in the presence of weak alkali. This enzyme resembles that which occurs in the large mononuclear cells of an inflammatory exudate and is more active than the similar enzyme of parenchymatons organs such as the liver. The enzyme which digests in the presence of acid exhibits greatest activity at a time when caseation is beginning. With advance of caseation its activity diminishes so that tissue which has undergone almost complete caseation exhibits trivial evidence of the presence of enzyme. It is probable that complete caseation is followed by total disappearance of enzymes. Tuberculous tissue contains an enzyme capable of digesting proteid in the presence of alkali (leucoprotease) only during the early stages of its development. This enzyme, present at a time when the tissue contains numerous polynuclear leucocytes, quickly disappears so that when enzyme digesting in acid is still active, leucoprotease has disappeared. The serum of a tuberculous pleural exudate obtained by intrapleural inoculation with tubercle bacilli causes slight inhibition of the mixture of enzymes contained in tuberculous tissue shortly after inoculation. The serum of blood causes complete inhibition of the enzymes contained in the same tuberculous tissue. Analysis of this difference indicates that the exuded tuberculous serum, like the serum of the blood, inhibits proteolysis caused by leucoprotease, but fails to inhibit digestion caused by an enzyme acting in the presence of acid. In testing this property of the exuded tuberculous serum lymphatic gland has been used because suitable tuberculous tissue has not been available. The serum of the tuberculous pleural exudate produced experimentally not only fails to exert the anti-enzymotic power which is exhibited by the serum of the blood, but is itself capable of causing active digestion of coagulated proteid. Normal blood serum does not digest proteid and the serum of a sterile inflammatory exudate obtained by injection of turpentine into the pleural cavity has caused very little digestion. The tests which have been made indicate that loss of anti-enzymotic power and ability to cause proteolysis increase with the age of the exudate. The foregoing facts offer suggestions which may serve to explain in part the nature of the tubercle and the changes which occur within it. The so-called epithelioid cells of the tubercle resemble the large mononuclear phagocytes of inflammatory exudates and both contain an enzyme of the same character. It is not improbable that caseation which, like autolysis, is accompanied by disappearance of nuclei is in part dependent upon the presence in the cells of this active proteolytic enzyme which is for a time held in check. Injury to cells by products of the tubercle bacillus or partial anæmia, the result of imperfect vascularization of the tuberculous tissue, may have a part in rendering these cells susceptible to self-digestion. Changes which have been observed in serum of the tuberculous exudate show that the anti-enzymotic property of the normal blood may be absent in the exudate of a tuberculous lesion. This loss of anti-enzymotic action, perhaps referable to changes caused by products of the tubercle bacillus, may favor self-digestion of the enzyme-containing cells and diffusion of their enzyme.

scholarly journals Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321731
Author(s):  
Dominik Aschenbrenner ◽  
Maria Quaranta ◽  
Soumya Banerjee ◽  
Nicholas Ilott ◽  
Joanneke Jansen ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Personalised Medicine ◽  
Mononuclear Phagocytes ◽  
Cytokine Network ◽  
Peripheral Blood Mononuclear ◽  
Transcriptional Signature ◽  
Inflammatory Monocytes ◽  
Transcriptomic Signature ◽  
Inflammatory Bowel

ObjectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.DesignWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.ResultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.ConclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

scholarly journals Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2516-2525 ◽  
Author(s):  
K Meszaros ◽  
S Aberle ◽  
R Dedrick ◽  
R Machovich ◽  
A Horwitz ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Binding Protein ◽  
Mononuclear Phagocytes ◽  
Factor Vii ◽  
Peripheral Blood Mononuclear ◽  
Recombinant Fragment

Abstract Mononuclear phagocytes, stimulated by bacterial lipopolysaccharide (LPS), have been implicated in the activation of coagulation in sepsis and endotoxemia. In monocytes LPS induces the synthesis of tissue factor (TF) which, assembled with factor VII, initiates the blood coagulation cascades. In this study we investigated the mechanism of LPS recognition by monocytes, and the consequent expression of TF mRNA and TF activity. We also studied the inhibition of these effects of LPS by rBPI23, a 23-kD recombinant fragment of bactericidal/permeability increasing protein, which has been shown to antagonize LPS in vitro and in vivo. Human peripheral blood mononuclear cells, or monocytes isolated by adherence, were stimulated with Escherichia coli O113 LPS at physiologically relevant concentrations (> or = 10 pg/mL). The effect of LPS was dependent on the presence of the serum protein LBP (lipopolysaccharide-binding protein), as shown by the potentiating effect of human recombinant LBP or serum. Furthermore, recognition of low amounts of LPS by monocytes was also dependent on CD14 receptors, because monoclonal antibodies against CD14 greatly reduced the LPS sensitivity of monocytes in the presence of serum or rLBP. Induction of TF activity and mRNA expression by LPS were inhibited by rBPI23. The expression of tumor necrosis factor showed qualitatively similar changes. Considering the involvement of LPS-induced TF in the potentially lethal intravascular coagulation in sepsis, inhibition of TF induction by rBPI23 may be of therapeutic benefit.

scholarly journals Increased in vitro and in vivo generation of procoagulant activity (tissue factor) by mononuclear phagocytes after intralipid infusion in rabbits

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1391-1395 ◽  
Author(s):  
P Montemurro ◽  
A Lattanzio ◽  
G Chetta ◽  
L Lupo ◽  
L Caputi-Iambrenghi ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Mononuclear Cells ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Procoagulant Activity ◽  
Sterile Saline ◽  
Functional Changes ◽  
Before And After

Abstract Intralipid, a fat emulsion widely used in parenteral nutrition, can produce marked functional changes of the mononuclear phagocyte system. We investigated the effect of Intralipid administration on the generation of procoagulant activity by rabbit mononuclear phagocytes. Two groups of ten rabbits given either a single infusion of Intralipid 10% or a similar volume of sterile saline were studied before and after infusion. Procoagulant activity was measured on isolated blood mononuclear cells after incubation with and without endotoxin, using a one-stage clotting assay. Cells from animals infused with Intralipid produced significantly more procoagulant activity than controls (P less than .01). Results were similar when freshly collected whole blood was incubated with and without endotoxin, and procoagulant activity was measured on subsequently isolated mononuclear cells (P less than .01). In addition, when rabbits were given a single injection of endotoxin, blood and spleen mononuclear cells harvested 50 to 60 minutes after the injection from animals pretreated with Intralipid expressed five to seven times more procoagulant activity than did cells from animals pretreated with saline. In all instances, procoagulant activity was identified as tissue factor. These findings suggest that Intralipid may cause functional changes in mononuclear phagocytes, resulting in increased production of tissue factor on incubation in short-term culture in vitro and in response to endotoxin in vivo.

scholarly journals In vivo production of interleukin-5, granulocyte-macrophage colony- stimulating factor, macrophages colony-stimulating factor, and interleukin-6 during intravenous administration of high-dose interleukin-2 in cancer patients [see comments]

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1981-1987 ◽  
Author(s):  
MR Schaafsma ◽  
JH Falkenburg ◽  
JE Landegent ◽  
N Duinkerken ◽  
S Osanto ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Interleukin 2 ◽  
Mononuclear Phagocytes ◽  
High Dose ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Stimulating Factor

Abstract Recombinant human interleukin-2 (IL-2), administered to cancer patients by continuous intravenous (IV) infusion (3 x 10(6) U/m2/d), was found to induce the in vivo production of colony-stimulating factors (CSF). Plasma obtained from patients during IL-2 treatment stimulated in vitro colony formation of normal human bone marrow cells, depleted of mononuclear phagocytes and T lymphocytes. This colony-stimulating activity (CSA) was identified as IL-5, granulocyte-macrophage CSF (GM- CSF), and macrophage CSF (M-CSF), by the ability of specific antibodies against these factors to neutralize their effects. The presence of IL-2- induced GM-CSF and M-CSF was also demonstrated by specific radioimmunoassays. During IL-2 treatment, plasma also contained detectable levels of IL-6, which was measured in a bioassay. Using a cDNA-polymerase chain reaction (PCR) with specific primer sets for the various CSF, we showed that IL-2 treatment induced the expression of mRNA for M-CSF, GM-CSF, IL-3, and IL-5, but not for granulocyte CSF (G- CSF) in peripheral blood mononuclear cells, suggesting differential expression of CSF in vivo in response to IL-2. Furthermore, no negative regulators of hematopoiesis, such as interferon gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha), were found in plasma. These data illustrate that in vivo administration of high-dose IL-2 may result in a stimulatory effect on hematopoiesis. The induction of detectable levels of IL-5 and GM-CSF in the circulation may explain the eosinophilia and neutrophilia observed in these patients.

scholarly journals Interferon (IFN)-α Activation of Human Blood Mononuclear Cells In Vitro and In Vivo for Nitric Oxide Synthase (NOS) Type 2 mRNA and Protein Expression: Possible Relationship of Induced NOS2 to the Anti–Hepatitis C Effects of IFN-α In Vivo

1997 ◽  
Vol 186 (9) ◽  
pp. 1495-1502 ◽  
Author(s):  
Ala I. Sharara ◽  
Douglas J. Perkins ◽  
Mary A. Misukonis ◽  
Stanley U. Chan ◽  
Jason A. Dominitz ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Mononuclear Cell ◽  
Mononuclear Cells ◽  
Mononuclear Phagocytes ◽  
No Production ◽  
Hepatitis C Infection ◽  
Serum Alanine Aminotransferase

Although researchers have noted high level activation of rodent mononuclear phagocytes for nitric oxide (NO) synthase type 2 (S2) expression and NO production with a variety of agents such as interferon (IFN) γ and endotoxin, it has been difficult to demonstrate activation of human mononuclear phagocytes. The purpose of this study was to determine if IFN-α serves as an activator in vitro and in vivo in humans. Treatment of normal monocytes or mononuclear cells in vitro with IFN-α caused a dose-dependent increase in monocyte NOS2 activity and NO production, and increased expression of NOS2 protein and mRNA expression. To determine if in vivo administration of IFN-α also modulated NOS2, we studied blood cells from patients with hepatitis C before and after IFN-α therapy. Untreated patients with chronic hepatitis C virus infection had levels of NOS activity and NOS2 antigen in freshly isolated mononuclear cells similar to those of healthy subjects, and they expressed minimal or no NOS2 mRNA. However, IFN-α treatment of patients with hepatitis C infection was associated with a significant elevation in mononuclear cell NOS activity, NOS2 antigen content, and NOS2 mRNA content. IFN-α–treated patients had significant decreases in levels of serum alanine aminotransferase and plasma hepatitis C mRNA. The degree of IFN-α–enhanced mononuclear cell NOS2 antigen content correlated significantly with the degree of reduction in serum alanine aminotransferase levels. Thus, IFN-α treatment of cells in vitro or administration of IFN-α to hepatitis C patients in vivo increases expression of mononuclear cell NOS2 mRNA expression, NOS activity, NOS2 antigen expression, and NO production. Since NO has been reported to have antiviral activity for a variety of viruses, we speculate that induced NO production may be related to the antiviral action(s) of IFN-α in hepatitis C infection.

scholarly journals Stimulation of prostacyclin synthesis in vascular cells by mononuclear cell products

Blood ◽  
1984 ◽  
Vol 64 (6) ◽  
pp. 1280-1283 ◽  
Author(s):  
E Dejana ◽  
F Breviario ◽  
G Balconi ◽  
V Rossi ◽  
G Remuzzi ◽  
...  
Keyword(s):  
Mononuclear Cell ◽  
Acid Metabolism ◽  
Mononuclear Cells ◽  
Vascular Tissue ◽  
Human Peripheral Blood ◽  
Arachidonic Acid Metabolism ◽  
Peripheral Blood Mononuclear ◽  
Aortic Smooth Muscle ◽  
Prostacyclin Synthesis ◽  
By Products

Abstract Supernatants were obtained from human peripheral blood mononuclear cells stimulated with phytohemagglutinin or in a mixed lymphocyte reaction. The effect of mononuclear cell products on vascular prostacyclin (PGI2) production was measured using cultured rat aortic smooth muscle cells (SMC) or aortic rings. PGI2 was measured by radioimmunoassay of its metabolite, 6-keto-PGF1 alpha. Supernatants containing mononuclear cell products induced PGI2 production in vascular tissue. Supernatant-induced PGI2 production of SMC was relatively slow, requiring more than six hours of incubation with supernatants, and was completely prevented by aspirin, a cyclooxygenase inhibitor. The regulation of arachidonic acid metabolism by products of stimulated mononuclear cells, which is critical to the physiology and pathology of blood vessels, may be an important aspect of the interaction between immunocompetent cells and vascular tissue.

scholarly journals Distribution of cells bearing receptors for a colony-stimulating factor (CSF-1) in murine tissues.

1981 ◽  
Vol 91 (3) ◽  
pp. 848-853 ◽  
Author(s):  
P V Byrne ◽  
L J Guilbert ◽  
E R Stanley
Keyword(s):  
Bone Marrow ◽  
Binding Sites ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Mononuclear Phagocytes ◽  
Small Cells ◽  
Phagocytic Cells ◽  
Alveolar Cells ◽  
Peritoneal Cells ◽  
Blood Mononuclear Cells

CSF-1 is a subclass of the colony-stimulating factors that specifically stimulates the growth of mononuclear phagocytes. We used the binding of 125I-CSF-1 at 0 degrees C by single cell suspensions from various murine tissues, in conjunction with radioautography, to determine the frequency of binding cells, their identity, and the number of binding sites per binding cell. For all tissues examined, saturation of binding sites was achieved within 2 h at 2--3 x 10(-10) M 125I-CSF-1. The binding was irreversible and almost completely blocked by a 2 h preincubation with 5 x 10(-10) M CSF-1. 125I-CSF-1 binding was exhibited by 4.3% of bone marrow cells, 7.5% of blood mononuclear cells, 2.4% of spleen cells, 20.5% of peritoneal cells, 11.8% of pulmonary alveolar cells and 0.4% of lymph node cells. Four morphologically distinguishable cell types bound 125I-CSF-1: blast cells; mononuclear cells with a ratio of nuclear to cytoplasmic area (N/C) greater than 1; cells with indented nuclei; and mononuclear cells with N/C less than or equal to 1. No CSF-1 binding cells were detected among blood granulocytes or thymus cells. Bone marrow promyelocytes, myelocytes, neutrophilic granulocytes, eosinophilic granulocytes, nucleated erythroid cells, enucleated erythrocytes, and megakaryocytes also failed to bind. The frequency distribution of grain counts per cell for blood mononuclear cells was homogenous. In contrast, those for bone marrow, spleen, alveolar, and peritoneal cells were heterogeneous. The monocytes in blood or bone marrow (small cells, with either indented nuclei or with N/C greater than 1) were relatively uniformly labeled, possessing approximately 3,000 binding sites per cell. Larger binding cells (e.g., alveolar cells) may possess higher numbers of receptors. It is concluded that CSF-1 binding is restricted to mononuclear phagocytic cells and their precursors and that it can be used to identify both mature and immature cells of this series.

scholarly journals A mononuclear cell component in experimental immunological glomerulonephritis.

1978 ◽  
Vol 147 (2) ◽  
pp. 369-384 ◽  
Author(s):  
G F Schreiner ◽  
R S Cotran ◽  
V Pardo ◽  
E R Unanue
Keyword(s):  
Experimental Model ◽  
Mononuclear Cell ◽  
Mononuclear Cells ◽  
Rat Kidney ◽  
Mononuclear Phagocytes ◽  
Cell Infiltrate ◽  
Cell Component ◽  
Neutrophilic Infiltration ◽  
Rabbit Igg ◽  
Monocytes And Macrophages

An accelerated form of nephrotoxic serum nephritis in the rat was examined. The experimental model consisted of preimmunization of the rat with rabbit IgG 5 days before injection of subnephrotoxic doses of rabbit anti-rat kidney serum. The immunized rats developed proteinuria during the first 24 h, increasing by 48-96 h. The early 24-h proteinuria correlated with a neutrophilic infiltration of glomeruli and with deposition of rat Ig and C. The 48- to 96-h proteinuria was associated with a glomerular infiltration by mononuclear cells and proliferation of intrinsic glomerular cells. Many of the mononuclear cells were morphologically identical to monocytes and macrophages. [3H]thymidine labeling experiments indicated that the mononuclear cells originated from dividing precursors localized outside the kidney. Preimmunized rats given systemic irradiation (the kidney being protected by a shield) showed loss of the mononuclear cell infiltrate and absence of 48- to 96-h proteinuria. We conclude that mononuclear phagocytes can infiltrate the kidney in immunological glomerular disease and might contribute to the functional abnormalities.

scholarly journals ENHANCED PASSIVE IMMUNITY TO STREPTOCOCCUS INFECTION IN RABBITS

1930 ◽  
Vol 52 (1) ◽  
pp. 95-102 ◽  
Author(s):  
F. P. Gay ◽  
A. R. Clark
Keyword(s):  
Mononuclear Cells ◽  
Normal Animal ◽  
Passive Immunity ◽  
Slight Effect ◽  
Degree Of Protection ◽  
Large Numbers ◽  
The Common ◽  
Cell Mobilization ◽  
High Degree ◽  
Pleural Exudate

The experimental work herein reported tends to justify our hypothesis recently expressed, that the common failure of antibacterial serums to combat active infections when passively transferred to a normal animal, is due not so much to a lack of suitable or sufficient antibodies as to absence of cell preparation or mobilization in the recipient. In the case of experimental streptococcus empyema in the rabbit the course of the ordinarily fatal infection is in no wise affected by the transfer of the pleural fluid containing large numbers of mononuclear cells derived from an animal that is itself protected as a result of a non-specific irritation. The serum of a rabbit highly immunized against the streptococcus and containing antibodies for it, produces relatively slight effect in prevention or cure. In contrast to this the pleural exudate, either acute (polymorphonuclear) or subacute (mononuclear), produced in an actively immunized animal does protect passively to a considerable degree. In a similar fashion normal exudate cells of either type in combination with the relatively ineffective antiserum give a high degree of protection. It remains for further analysis to determine whether this form of passive immunity by antiserum enhanced by the addition of cells depends on the vital properties of the cells transferred or on their stimulation to cell mobilization in the recipient. And furthermore the extent to which this enhanced passive immunity may be effective in cure, and whether the cure is applicable to local or to both local and generalized infection remains to be seen.

scholarly journals In vivo production of interleukin-5, granulocyte-macrophage colony- stimulating factor, macrophages colony-stimulating factor, and interleukin-6 during intravenous administration of high-dose interleukin-2 in cancer patients [see comments]

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1981-1987
Author(s):  
MR Schaafsma ◽  
JH Falkenburg ◽  
JE Landegent ◽  
N Duinkerken ◽  
S Osanto ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Interleukin 2 ◽  
Mononuclear Phagocytes ◽  
High Dose ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Stimulating Factor

Recombinant human interleukin-2 (IL-2), administered to cancer patients by continuous intravenous (IV) infusion (3 x 10(6) U/m2/d), was found to induce the in vivo production of colony-stimulating factors (CSF). Plasma obtained from patients during IL-2 treatment stimulated in vitro colony formation of normal human bone marrow cells, depleted of mononuclear phagocytes and T lymphocytes. This colony-stimulating activity (CSA) was identified as IL-5, granulocyte-macrophage CSF (GM- CSF), and macrophage CSF (M-CSF), by the ability of specific antibodies against these factors to neutralize their effects. The presence of IL-2- induced GM-CSF and M-CSF was also demonstrated by specific radioimmunoassays. During IL-2 treatment, plasma also contained detectable levels of IL-6, which was measured in a bioassay. Using a cDNA-polymerase chain reaction (PCR) with specific primer sets for the various CSF, we showed that IL-2 treatment induced the expression of mRNA for M-CSF, GM-CSF, IL-3, and IL-5, but not for granulocyte CSF (G- CSF) in peripheral blood mononuclear cells, suggesting differential expression of CSF in vivo in response to IL-2. Furthermore, no negative regulators of hematopoiesis, such as interferon gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha), were found in plasma. These data illustrate that in vivo administration of high-dose IL-2 may result in a stimulatory effect on hematopoiesis. The induction of detectable levels of IL-5 and GM-CSF in the circulation may explain the eosinophilia and neutrophilia observed in these patients.

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