scholarly journals Secretion of lysosomal hydrolases by stimulated and nonstimulated macrophages.

1978 ◽  
Vol 148 (2) ◽  
pp. 435-450 ◽  
Author(s):  
J Schnyder ◽  
M Baggiolini
Keyword(s):  
Plasminogen Activator ◽  
Lysosomal Enzyme ◽  
Peritoneal Macrophages ◽  
Enzyme Secretion ◽  
Wall Material ◽  
Lysosomal Hydrolases ◽  
Intracellular Enzyme ◽  
Proteose Peptone ◽  
Peptone Medium

Peritoneal macrophages were obtained from untreated mice and from mice treated with thioglycollate medium (TA), proteose peptone medium (PP), or a suspension of streptococcus A cell wall material (SA). The biochemical and secretory properties of these cells in long term cultures (up to 2 wk) were compared. TA-elicited macrophages contained more protein, lactate dehydrogenase, lysosomal hydrolases, and in particular, more plasminogen activator than the other cells studied. All types of macrophages studied were found to release considerable amounts of lysosomal hydrolases (beta-glucuronidase, N-acetyl-beta-glucosaminidase, alpha-mannosidase, and acid phosphatase) into the medium. Release was independent of phagocytosis and must, therefore, be regarded as true secretion. In both elicited and nonelicited macrophages, the rates of lysosomal enzyme secretion were virtually identical in the presence and in the absence of serum, and they were not enhanced by increasing serum concentrations. Lysosomal enzyme secretion in macrophages appears to depend on protein synthesis, since it was blocked by low concentrations of cycloheximide which neither affected cell viability nor lowered the intracellular enzyme levels. The amounts of lysosomal hydrolases secreted were highest in TA-elicited macrophages. The rates of secretion of PP- or SA-elicited and of nonelicited macrophages were about one-fourth of that of the TA-elicited cells. This difference, although significant, is much smaller than that observed for the secretion of plasminogen activator which was 20-50 times higher in TA-elicited cells. Acid glycosidases were also found in the peritoneal lavage media used for cell harvesting from both treated and nontreated mice. This indicates that active secretion of lysosomal hydrolases may be an in vivo property of the macrophage.

Microtubule modulation of biliary excretion of endogenous and exogenous hepatic lysosomal constituents

1984 ◽  
Vol 246 (1) ◽  
pp. G8-G15 ◽  
Author(s):  
R. B. Sewell ◽  
S. S. Barham ◽  
A. R. Zinsmeister ◽  
N. F. LaRusso
Keyword(s):  
Lysosomal Enzyme ◽  
Biliary Excretion ◽  
Lysosomal Enzymes ◽  
Male Rats ◽  
Enzyme Secretion ◽  
Initial Increase ◽  
Acute Administration ◽  
Subsequent Decrease ◽  
Before And After

We tested the hypothesis that hepatocyte microtubules modulate the biliary excretion of endogenous and exogenous constituents of hepatocyte lysosomes. We collected bile via bile fistulas from male rats before and after acute administration of colchicine and vinblastine, agents known to bind to hepatocyte microtubules; rats were then killed and livers were homogenized for biochemical analyses or processed for electron microscopy. Colchicine caused biphasic, parallel alterations in the biliary excretion of three lysosomal enzymes compared with control rats given saline or lumicolchicine; a peak rise in enzyme outputs of approximately 175% at 45-60 min after colchicine administration was followed by a sustained fall to approximately 25% of control values, which persisted for 2-4 h. When hepatocyte lysosomes were prelabeled in vivo by administration of [3H]Triton WR-1339, a nonionic detergent that is sequestered in hepatic lysosomes, the biliary excretion of radiolabel in response to colchicine paralleled the biliary excretion of the three lysosomal enzymes. Vinblastine also induced a biphasic response in biliary lysosomal enzyme output that was similar to that produced by colchicine administration. Morphometric analysis of electron micrographs of rat livers demonstrated changes in the number of lysosomelike vesicles in the vicinity of bile canaliculi after colchicine and vinblastine administration; the initial increase in lysosomal enzyme secretion was associated with a significant decrease in the number of pericanalicular lysosomes after both agents, while the subsequent decrease in enzyme secretion coincided with an increase in the number of pericanalicular lysosomes after vinblastine.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Spontaneous lysosomal enzyme secretion by a murine macrophage-like cell line

1980 ◽  
Vol 190 (3) ◽  
pp. 847-850 ◽  
Author(s):  
W Jessup ◽  
R T Dean
Keyword(s):  
Cell Line ◽  
Lysosomal Enzyme ◽  
Peritoneal Macrophages ◽  
Enzyme Secretion ◽  
Murine Macrophage ◽  
Lysosomal Hydrolase

Lysosomal enzyme secretion by the murine macrophage-like cell line, P388D1, was compared with that of normal peritoneal macrophages. Unlike macrophages, lysosomal hydrolase secretion by P388D1 cells occurred spontaneously in vitro and was not further stimulated by the presentation of inflammatory agents such as zymosan and asbestos.

scholarly journals Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ping Zeng ◽  
Bin Liu ◽  
Qun Wang ◽  
Qin Fan ◽  
Jian-Xin Diao ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasminogen Activator Inhibitor ◽  
Peritoneal Macrophages ◽  
Potential Binding Site ◽  
Induced Apoptosis ◽  
Activator Inhibitor

Macrophage survival is believed to be a contributing factor in the development of early atherosclerotic lesions. Dysregulated apoptosis of macrophages is involved in the inflammatory process of atherogenesis. Apigenin is a flavonoid that possesses various clinically relevant properties such as anti-inflammatory, antiplatelet, and antitumor activities. Here we showed that apigenin attenuated atherogenesis inapoE-/-mice in anin vivotest.In vitroexperiments suggested that apigenin induced apoptosis of oxidized low density lipoprotein- (OxLDL-) loaded murine peritoneal macrophages (MPMs). Proteomic analysis showed that apigenin reduced the expression of plasminogen activator inhibitor 2 (PAI-2). PAI-2 has antiapoptotic effects in OxLDL-loaded MPMs. Enhancing PAI-2 expression significantly reduced the proapoptosis effects of apigenin. Molecular docking assay with AutoDock software predicted that residue Ser473 of Akt1 is a potential binding site for apigenin. Lentiviral-mediated overexpression of Akt1 wild type weakened the proapoptosis effect of apigenin in OxLDL-loaded MPMs. Collectively, apigenin executes its anti-atherogenic effects through inducing OxLDL-loaded MPMs apoptosis. The proapoptotic effects of apigenin were at least partly attributed to downregulation of PAI-2 through suppressing phosphorylation of AKT at Ser473.

Activated macrophages in highly irradiated cercariae-induced immunity toSchistosoma japonicumin rats

Parasitology ◽  
1991 ◽  
Vol 102 (1) ◽  
pp. 65-72
Author(s):  
C. Xu ◽  
S. Xu
Keyword(s):  
Alveolar Macrophages ◽  
Sheep Erythrocyte ◽  
Peritoneal Macrophages ◽  
Rat Serum ◽  
Sheep Erythrocytes ◽  
Proteose Peptone ◽  
Normal Rat ◽  
Induced Immunity

SUMMARYThe results of studies on the schistosomulicidal activity of activated peritoneal and alveolar macrophages (pMø and aMø) from rats immunized with highly irradiated (50 krad.)Schistosoma japonicumcercariae are reported. The authors have examined the activation of these macrophages in terms of spreading, adhesion and ingestion of sheep erythrocytes and pinocytosis of horse-radish peroxidase. Using three criteria, peritoneal macrophages and alveolar macrophages from immunized rats and from rats intraperitoneally injected with BCG were significantly more active than those from normal rats or rats stimulated with 10% proteose-peptone or 1% sodium thioglycolate. A significantly higher percentage of adhesion and ingestion was obtained with the sheep erythrocytes that were co-opsonized by heat-inactivated rat anti-sheep erythrocyte serum and fresh normal rat serum. Schistosomulicidal effects were observed with macrophages from irradiated cercariae-immunized rats in two activation systems:in vitroactivation in the presence of macrophage-activating factor (MAF), andin vivoactivation by the intraperitoneal challenge with sonicated cercarial antigens.

scholarly journals Trypanosoma cruzi: the immunological induction of macrophage plasminogen activator requires thymus-derived lymphocytes.

1977 ◽  
Vol 146 (1) ◽  
pp. 172-183 ◽  
Author(s):  
N Nogueira ◽  
S Gordon ◽  
Z Cohn
Keyword(s):  
Trypanosoma Cruzi ◽  
Spleen Cell ◽  
Plasminogen Activator ◽  
Peritoneal Macrophages ◽  
Enzyme Secretion ◽  
Cell Populations ◽  
Spleen Cells ◽  
Trypanocidal Activity ◽  
Mouse Peritoneal Macrophages

In this article we describe methods in which unstimulated mouse peritoneal macrophages were induced to secrete high livels of plasminogen activator under in vitro conditions. The exposure of sensitized peritoneal or spleen cell populations from Trypanosoma cruzi-infected animals to either viable or heat-killed trypanosomes lead to the release of an inducing factor(s). Maximal levels of plasminogen activator secretion are achieved by the incubation of such factors (s) with unstimulated macrophages for 48 h. A significant increase in enzyme secretion was already observed after a 24 h incubation. The production of the inducing factor(s) by sensitized cells was immunologically specific and unrelated antigens did not stimulate the production of the factor(s) by sensitized peritoneal or spleen cell populations. The inducing factor(s) was produced by nylon-wool-fractionated spleen and peritoneal cells which had been depleted of marcrophages. Pretreatment of sensitized spleen cells with anti-theta serum and C abolished the production of the activating factor(s). The active supernatant fluids were able to induce secretion of macrophage plasminogen activator across H-2 barriers. Attempts to induce trypanocidal activity in unstimulated macrophages have not been successful.

Effects of chloroquine and methylamine on lysosomal enzyme secretion by rat pancreas

1992 ◽  
Vol 262 (3) ◽  
pp. G439-G444
Author(s):  
T. Hirano ◽  
A. Saluja ◽  
P. Ramarao ◽  
M. M. Lerch ◽  
M. L. Steer
Keyword(s):  
Lysosomal Enzyme ◽  
Cathepsin B ◽  
Secretory Pathway ◽  
Amylase Secretion ◽  
Zymogen Granule ◽  
Lysosomal Hydrolases ◽  
Pancreatic Acini ◽  
Lysosomotropic Agents

In vivo pancreatic secretion of the lysosomal hydrolase cathepsin B was found to be increased by infusion of the secretagogue caerulein. The basal as well as caerulein-stimulated in vivo rate of cathepsin B was further increased by infusion of either chloroquine or methylamine while neither the basal nor the secretagogue-stimulated rates of amylase secretion were altered by the lysosomotropic agents. These observations indicate that neutralization of the acidic prelysosomal compartment by administration of lysosomotropic agents results in lysosomal enzyme entry, by default, into the regulated secretory pathway. In vitro stimulation of pancreatic acini with caerulein was also found to stimulate cathepsin B secretion. That in vitro rate of cathepsin B secretion stimulated by caerulein was not increased in acini prepared from animals infused with caerulein, chloroquine, or methylamine, but the in vitro rate of cathepsin B secretion stimulated by caerulein was increased in acini prepared from animals infused with caerulein plus either chloroquine or methylamine. Under these conditions, redistribution of cathepsin B from the lysosome-enriched to the zymogen granule-enriched subcellular fraction was noted, and lysosomal enzyme-containing organelles became increasingly fragile. These observations indicate that in vivo secretagogue stimulation increases the degree of diversion of lysosomal hydrolases into the regulated secretory compartment when the prelysosomal compartment has been neutralized with lysosomotropic agents.

scholarly journals Release of Fibrinolytic Enzymes by Macrophages in Response to Soluble Fibrin

1977 ◽  
Author(s):  
L. A. Sherman ◽  
J. Lee ◽  
C. C. Stewart
Keyword(s):  
Plasminogen Activator ◽  
Proteolytic Enzymes ◽  
Peritoneal Macrophages ◽  
Phagocytic Cells ◽  
Fibrinolytic Enzymes ◽  
Soluble Fibrin ◽  
The Media ◽  
Free Media

In previous data (J. Exp. Med. 147:76,1977), we have demonstrated that soluble fibrin/fibrinogen complexes are bound to the plasma membrane of guinea pig peritoneal macrophages. This binding is largely irreversible and is not a result of phagocytosis. We have extended our studies to examine the response in vitro of peritoneal macrophages to soluble fibrin/fibrinogen complexes. Unstimulated mouse macrophages were collected by peritoneal lavage and 5–60 μg of soluble fibrin/fibrinogen complexes placed into tissue culture dishes containing the unstimulated cells. Aliquots of the media were collected at 24, 48 and 72 hours. The cell-free media contained increasing amounts both of plasminogen activator and an enzymatic activity which resulted in fibrin and fibrinogen proteolysis independent of the amount of plasmingoen present. The major proteolytic activity was due to the non-plasminogen dependent enzyme. Similar enzymes were released from peritoneal macrophages stimulated in vivo. The plasminogen activator enzyme had a low molecular weight comparable to that previously reported by Unkeless et al, with in vivo stimulation. Other coagulation moieties, such as plasmin and α-2 macroglobulin plasmin complexes did not result in release of the macrophage proteolytic enzymes. The results suggest that the previously described release of fibrinolytic enzymes after thioglycolate injections, may also result from the more pathophysiological stimulation by soluble fibrin/fibrinogen complexes. Release of these enzymes from phagocytic cells may be important, not only in blood clearance of soluble fibrin/fibrinogen complexes, but as part of thrombus reabsorption and wound healing.

scholarly journals Glucan receptor and zymosan-induced lysosomal enzyme secretion in macrophages

1995 ◽  
Vol 306 (3) ◽  
pp. 829-835 ◽  
Author(s):  
H Tapper ◽  
R Sundler
Keyword(s):  
Lysosomal Enzyme ◽  
Intracellular Signaling ◽  
Peritoneal Macrophages ◽  
Secretory Response ◽  
Enzyme Secretion ◽  
Cell Contact ◽  
Beta Glucan ◽  
High Particle ◽  
Mouse Peritoneal Macrophages ◽  
Multiple Interactions

A receptor for beta-glucan was in the present study shown to mediate binding of zymosan particles to resident mouse peritoneal macrophages. Lysosomal enzyme secretion in response to zymosan was maximal at a low particle/cell ratio, continuous for at least 3 h after particle/cell contact and inhibitable by soluble glucan. Latex particles of various size caused no selective secretory response, but at high particle/cell ratios were toxic. By use of a fluorescent ligand, the macrophage beta-glucan receptor was shown to be trypsin-sensitive, Ca2+/Mg(2+)-independent, recirculating and also present in an intracellular mobilizable pool. Binding of ligand to the beta-glucan receptor and inhibition of the lysosomal secretory response to zymosan were both more efficient with glucans of larger size, indicating that clustering of glucan receptors at the cell surface occurs. Such clustering could stabilize ligand binding by multiple interactions and possibly trigger intracellular signaling events on binding of zymosan particles.

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