scholarly journals Suppression of monocyte and neutrophil function by recombinant IL-2

1993 ◽  
Vol 2 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Susan E. Smith ◽  
Gayle D. Warren ◽  
Yee-Hing Thong ◽  
Joe G. McCormack
Keyword(s):  
Glucose Uptake ◽  
Neutrophil Migration ◽  
Neutrophil Function ◽  
Biologically Active ◽  
Hexose Monophosphate ◽  
Myristate Acetate ◽  
Hexose Monophosphate Shunt ◽  
Neutrophil Adherence ◽  
Dose Dependent ◽  
Monocyte Adherence

Little IS known about the influence of IL-2 on phagocytes. We now describe the effects of human recombinant IL-2 on human neutrophil and monocyte functions related to mobility, phagocytosis, glucose uptake, respiration and degranulation. Neutrophil adherence and hexose monophosphate shunt activities were both suppressed after incubation with IL-2. IL-2 had no effect on neutrophil migration, phagocytosis, deoxyglucose uptake or degranulation, ionocytes demonstrated a greater sensitivity to IL-2 with suppression of monocyte adherence, random and stimulated migration, glucose uptake and hexose monophosphate shunt activity, even after addition of phorbol myristate acetate. Monocyte phagocytosis and degranulation were not affected. All of the effects observed were dose-dependent within a biologically active range for IL-2. These studies suggest that IL-2 may have an important down-regulatory role across a broad range of monocyte functions including movement, deoxyglucose uptake and respiration. However, its role in regulation of neutrophil function is limited to adherence and respiration. IL-2 may be a more versatile cytokine than has previously been appreciated.

scholarly journals Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4

Blood ◽  
1984 ◽  
Vol 64 (4) ◽  
pp. 780-785
Author(s):  
JC Gay ◽  
JK Beckman ◽  
AR Brash ◽  
JA Oates ◽  
JN Lukens
Keyword(s):  
Neutrophil Function ◽  
Leukotriene B4 ◽  
Human Neutrophils ◽  
Neutrophil Chemotaxis ◽  
Myristate Acetate ◽  
Fmlp Receptor ◽  
Dose Dependent ◽  
O2 Production ◽  
Oxygen Metabolites ◽  
Oxidative Responses

Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.

scholarly journals Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4

Blood ◽  
1984 ◽  
Vol 64 (4) ◽  
pp. 780-785 ◽  
Author(s):  
JC Gay ◽  
JK Beckman ◽  
AR Brash ◽  
JA Oates ◽  
JN Lukens
Keyword(s):  
Neutrophil Function ◽  
Leukotriene B4 ◽  
Human Neutrophils ◽  
Neutrophil Chemotaxis ◽  
Myristate Acetate ◽  
Fmlp Receptor ◽  
Dose Dependent ◽  
O2 Production ◽  
Oxygen Metabolites ◽  
Oxidative Responses

Abstract Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.

scholarly journals Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes

Blood ◽  
1976 ◽  
Vol 47 (4) ◽  
pp. 545-554 ◽  
Author(s):  
LR DeChatelet ◽  
PS Shirley ◽  
RB Jr Johnston
Keyword(s):  
Phorbol Myristate Acetate ◽  
Oxidative Metabolism ◽  
Polymorphonuclear Leukocytes ◽  
Time Course ◽  
Human Neutrophils ◽  
Hexose Monophosphate ◽  
Myristate Acetate ◽  
Bacterial Killing ◽  
Hexose Monophosphate Shunt ◽  
Human Polymorphonuclear Leukocytes

The addition of 0.1 mug/ml of phorbol myristate acetate (PMA) to a suspension of resting human neutrophils causes a marked stimulation of all aspects of cellular oxidative metabolism normally associated with phagocytosis. PMA induces a greatly increased rate of glucose oxidation via the hexose monophosphate shunt, increased production of superoxide anion and of hydrogen peroxide, increased cellular chemiluminescence, and increased iodination of protein material. The time course of hexose monophosphate shunt activation and of chemiluminescence are similar to those observed following phagocytosis of opsonized zymosan; the levels of activation achieved in all cases approximate those seen following phagocytosis. These phenomena are not simply reflections of altered cellular permeability, since PMA actually inhibits the uptake of radioactive 2-deoxyglucose and of uniformly labeled amino acids. The addition of PMA similarly inhibits the uptake of 14C-labeled bacteria, suggesting a competition between the effect of the chemical and the process of phagocytosis. These results suggest that PMA activates the cell in the same manner as does phagocytosis. This compound should provide a useful tool for elucidating the metabolic events underlying the phenomena of phagocytosis and bacterial killing by polymorphonuclear leukocytes.

scholarly journals Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes

Blood ◽  
1976 ◽  
Vol 47 (4) ◽  
pp. 545-554 ◽  
Author(s):  
LR DeChatelet ◽  
PS Shirley ◽  
RB Jr Johnston
Keyword(s):  
Phorbol Myristate Acetate ◽  
Oxidative Metabolism ◽  
Polymorphonuclear Leukocytes ◽  
Time Course ◽  
Human Neutrophils ◽  
Hexose Monophosphate ◽  
Myristate Acetate ◽  
Bacterial Killing ◽  
Hexose Monophosphate Shunt ◽  
Human Polymorphonuclear Leukocytes

Abstract The addition of 0.1 mug/ml of phorbol myristate acetate (PMA) to a suspension of resting human neutrophils causes a marked stimulation of all aspects of cellular oxidative metabolism normally associated with phagocytosis. PMA induces a greatly increased rate of glucose oxidation via the hexose monophosphate shunt, increased production of superoxide anion and of hydrogen peroxide, increased cellular chemiluminescence, and increased iodination of protein material. The time course of hexose monophosphate shunt activation and of chemiluminescence are similar to those observed following phagocytosis of opsonized zymosan; the levels of activation achieved in all cases approximate those seen following phagocytosis. These phenomena are not simply reflections of altered cellular permeability, since PMA actually inhibits the uptake of radioactive 2-deoxyglucose and of uniformly labeled amino acids. The addition of PMA similarly inhibits the uptake of 14C-labeled bacteria, suggesting a competition between the effect of the chemical and the process of phagocytosis. These results suggest that PMA activates the cell in the same manner as does phagocytosis. This compound should provide a useful tool for elucidating the metabolic events underlying the phenomena of phagocytosis and bacterial killing by polymorphonuclear leukocytes.

Ecological and physiological as well as biochemical properties of representatives of the Genus sedum L.

2014 ◽  
Vol 25 (3-4) ◽  
pp. 24-33
Author(s):  
O. I. Dzjuba ◽  
M. V. Yatsenko
Keyword(s):  
Nitric Oxide ◽  
Cell Line ◽  
Methanol Extract ◽  
Hepatoma Cell ◽  
Ethanol Extract ◽  
Biochemical Properties ◽  
Biologically Active ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Dose Dependent

The article deals with the history of the study and the current state of research of physiological and biochemical properties of the plant genus Sedum that are useful for human and has been used in folk medicine for many years. It was noticed that antioxidant properties of extracts from plants S. sarmentosum, S. sempervivoides, S. takesimense were caused by the presence of phenolic compounds. Methanol extract of plants S. takesimense exhibited strong scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals as well as significant inhibitory effects on lipid peroxidation and low density lipoprotein (LDL) oxidation induced by a metal ion Cu2+. Various immunomodulatory activities of various fractions of plants extracts (S. dendroideum, S. kamtschaticum, S. sarmentosum, S. telephium) are observed. It was shown that the ethanol extract of S. sarmentosum and it’s fractions suppressed specific antibody and cellular responses to ovalbumin in mice. The methanol extract of plants S. sarmentosum reduced the levels of anti-inflammatory markers, such as volume of exudates, number of polymorphonuclear leukocytes, suppressed nitric oxide synthesis in activated macrophages via suppressed induction of inducible nitric oxide synthase (iNOS). Polysaccharides fractions from plants S. telephium inducing productions of tumor necrosis factor alpha (TNF-α), increasing the intensity of phagocytosis in vitro and in vivo. Methanol extract from the whole part of S. kamtschaticum strongly inhibit PGE2 production from lipopolysaccharide-induced RAW 264.7 cells, a mouse macrophage cell line via modulating activity in gene expression of the enzyme cyclooxygenase-2 (COX-2). The methanol extract of plants S. sarmentosum and the major kaempferol glycosides from S. dendroideum have antinociceptive activity. It was noticed that anti-adipogenic activity of extracts from plants S. kamtschaticum were caused by inhibition of peroxisome-proliferator-activated receptor γ (PPARγ) expression and it’s dependent target genes, such as genes encoding adipocyte protein 2 (аР2), lipoprotein lipase (LPL), adiponectin and CD36. Polysaccharides fractions from S. telephium cause inhibition of cell adhesion of human fibroblast (MRC5) to laminin and fibronectin via interfere with integrin-mediated cell behaviour and they contributed to the role of polysaccharides in cell-matrix interaction. The methanol extract of plants S. sarmentosum exhibited a significant inhibitory activity in the chick embryo chorioallantoic membrane angiogenesis in a dose-dependent manner. The crude alkaloid fraction of S. sarmentosum caused a dose-dependent inhibition of cell proliferation on murine hepatoma cell line BNL CL.2 and human hepatoma cell line HepG2 without necrosis or apoptosis. Alkaloids from plants S. sarmentosum may improve survival of hepatoma patients via the inhibition of excessive growth of tumor cells. Plant’s juices have antiviral activity (S. sarmentosum, S. spurium, S. stahlii). Crude ethanol extract S. praealtum have spermicidal activity of the in mice and a relevant inhibitory effect of aqueous extract on human spermatozoa motility as well as an anti-fertilizing activity in rats. Hepatoprotective triterpenes, e.g., δ-amyrone, 3-epi-δ-amyrin, δ-amyrin and sarmentolin were isolated from S. sarmentosum. 2- and 2,6-substituted piperidine alkaloids (e.g., norsedamine, allosedridine, sedamine, allosedamine) are observed in plants S. acre, which in the presence of data on the use of pyridine and piperidine derivatives for treating neurodegenerative diseases (e.g., Alzheimer's disease), points on the promising research in this area. Taking into account that biologically active compounds are accumulated in the aboveground vegetative organs of plants of Sedum, the prospects of further study of the use of Sedum for the purposes of biotechnology and in the pharmaceutical industry becomes apparent. This work extends the existing views regarding the use of plants Sedum.

Cytoplasmic pH regulation in phorbol ester-activated human neutrophils

1986 ◽  
Vol 251 (1) ◽  
pp. C55-C65 ◽  
Author(s):  
S. Grinstein ◽  
W. Furuya
Keyword(s):  
Metabolic Pathways ◽  
Phorbol Esters ◽  
Ph Regulation ◽  
Human Neutrophils ◽  
Hexose Monophosphate ◽  
Cytoplasmic Ph ◽  
Extracellular Acidification ◽  
Hexose Monophosphate Shunt ◽  
Activated Neutrophils ◽  
Cytoplasmic Acidification

Activation of neutrophils by 12-O-tetradecanoylphorbol-13-acetate (TPA) is accompanied by an initial cytoplasmic acidification, followed by an alkalinizing phase due to Na+-H+ countertransport. The source of the acidification, which is fully expressed by activation with TPA in Na+-free or amiloride-containing media, was investigated. The acidification phase was detected also in degranulated and enucleated cytoplasts, ruling out a major contribution by the nucleus or secretory vesicles. Cytoplasmic acidification was found to be associated with an extracellular acidification, suggesting metabolic generation of H+. Two principal metabolic pathways are stimulated in activated neutrophils: the reduction of O2 by NADPH-oxidase and the hexose monophosphate shunt. A good correlation was found between the activity of these pathways and the changes in cytoplasmic pH. Inhibition of superoxide synthesis prevented the TPA-induced cytoplasmic acidification. Moreover, activation of the hexose monophosphate shunt with permeable NADPH-oxidizing agents (in the absence of TPA) also produced a cytoplasmic acidification. Cytoplasmic acidification was also elicited by exogenous diacylglycerol and by other beta-phorbol diesters, which are activators of the kinase, but not by unesterified phorbol or by alpha-phorbol diesters, which are biologically inactive. The results suggest that the cytoplasmic acidification induced by phorbol esters in neutrophils reflects accumulation of H+ liberated during the metabolic burst that follows activation.

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