scholarly journals The effects of basic substances and acidic ionophores on the digestion of exogenous and endogenous proteins in mouse peritoneal macrophages.

1986 ◽  
Vol 102 (3) ◽  
pp. 959-966 ◽  
Author(s):  
S Ohkuma ◽  
J Chudzik ◽  
B Poole
Keyword(s):  
Bovine Serum Albumin ◽  
Enzyme Activities ◽  
Inhibitory Effect ◽  
Peritoneal Macrophages ◽  
The Other ◽  
Selective Effect ◽  
Lysosomal Ph ◽  
Endogenous Proteins ◽  
Mouse Peritoneal Macrophages ◽  
Basic Substances

Basic substances and acidic ionophores that increase the lysosomal pH in cultured macrophages (Ohkuma, S., and B. Poole, 1978, Proc. Natl. Acad. Sci. USA., 75:3327-3331; Poole, B., and S. Ohkuma, 1981, J. Cell Biol., 90:665-669) inhibited the digestion of heat-denatured acetylated bovine serum albumin (BSA) taken up by the cells. For several substances, the shift in pH sufficed to explain the inhibition of proteolysis. Additional effects, presumably on enzyme activities, have to be postulated for tributylamine, amantadine, and chloroquine. Sodium fluoride (10 mM) had no significant effect on the breakdown of BSA by macrophages. The breakdown of endogenous macrophage proteins, whether short lived or long lived, was inhibited approximately 40% by 10 mM NaF and 30%, or sometimes less in the case of long-lived proteins, by 100 microM chloroquine. When the cells were supplied with BSA, a mixture of cell proteins, or even inert endocytosible materials, the breakdown of endogenous long-lived proteins and the inhibitory effect of chloroquine on this process were selectively reduced. Inhibition of endocytosis by cytochalasins B or D did not affect the chloroquine-sensitive breakdown of endogenous proteins, indicating that the proteins degraded by this process were truly endogenous and not taken in from the outside by cellular cannibalism. On the other hand, when macrophage proteins were supplied extracellularly, their breakdown occurred at the same rate for short-lived and long-lived proteins, and it was strongly inhibited by chloroquine and not by NaF. It is concluded from these results that the breakdown of endogenous proteins, both short-lived and long-lived, probably takes place partly (approximately 30%) in lysosomes and partly through one or more nonlysosomal mechanism(s) unaffected by chloroquine and presumably susceptible to inhibition by fluoride. A difference must exist between short-lived and long-lived proteins in the manner in which they reach lysosomes or are handled by these organelles; this difference would account for the selective effect of the supply of endocytosible materials on the lysosomal processing of long-lived proteins.

A Protein-bound Polysaccharide Synergistic with Lipopolysaccharide Induces Nitric Oxide Release and Antioxidant Enzyme Activities in Mouse Peritoneal Macrophages

1998 ◽  
Vol 26 (02) ◽  
pp. 133-141 ◽  
Author(s):  
Zhan-Jun Pang ◽  
Mei Zhou ◽  
Yuan Chen ◽  
Jennifer Wan
Keyword(s):  
Nitric Oxide ◽  
Enzyme Activities ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Peritoneal Macrophages ◽  
Treated Mouse ◽  
Antioxidant Enzyme Activities ◽  
Sod Activity ◽  
Nitric Oxide Release ◽  
Mouse Peritoneal Macrophages

The aim of this study is to examine whether polysaccharide krestin, a protein-bound polysaccharide, can prevent the progression of therosclerosis and lipoperoxidative injury caused by oxidatively modified low density lipoprotein (Ox-LDL) to macrophages. The alterations of GSHPx (glutathione peroxidase), SOD (superoxide dismutase) activity and NO (nitric oxide) release in PSK-treated mouse peritoneal macrophages, and the effect of LPS on them were investigated. With peritoneal injection of PSK, the following were observed in the mouse peritoneal macrophages: 1) an increase in SeGSHPx activity, 2) elevation in non-SeGSHPx and SOD activity; 3) the enzyme activities were further improved by addition of lipopolysaccharide (LPS); and 4) much NO was found to be released by PSK-treated mouse peritoneal macrophages stimulated by LPS.

scholarly journals Degradation of connective tissue matrices by macrophages. II. Influence of matrix composition on proteolysis of glycoproteins, elastin, and collagen by macrophages in culture.

1980 ◽  
Vol 152 (6) ◽  
pp. 1527-1536 ◽  
Author(s):  
P A Jones ◽  
Z Werb
Keyword(s):  
Connective Tissue ◽  
Peritoneal Macrophages ◽  
The Other ◽  
Matrix Proteins ◽  
Matrix Composition ◽  
Disease States ◽  
The Matrix ◽  
Rate Of Hydrolysis ◽  
Hydrolysis Of ◽  
Mouse Peritoneal Macrophages

Thioglycollate-elicited mouse peritoneal macrophages were cultured in contact with the mixture of extracellular matrix proteins produced by rat smooth muscle cells in culture. Both live macrophages and their conditioned media hydrolyzed glycoproteins, elastin, and collagen. Live macrophages also degraded extracellular connective tissue proteins secreted by endothelial cells and fibroblasts. The glycoproteins in the matrix markedly inhibited the rate of digestion of the other macromolecules, particularly elastin. When plasminogen was added to the matrix, activation of plasminogen to plasmin resulted in the hydrolysis of the glycoprotein components, which then allowed the macrophage elastase easier access to its substrate, elastin. Thus, although plasmin has no direct elastinolytic activity, its presence accelerated the rate of hydrolysis of elastin and therefore the rate of matrix degradation. These findings may be important in an understanding of disease states, such as emphysema and atherosclerosis, that are characterized by the destruction of connective tissue.

scholarly journals The selective release of phospholipase A2 by resident mouse peritoneal macrophages

1981 ◽  
Vol 200 (2) ◽  
pp. 441-444 ◽  
Author(s):  
P D Wightman ◽  
M E Dahlgren ◽  
P Davies ◽  
R J Bonney
Keyword(s):  
Phospholipase A2 ◽  
Phospholipase C ◽  
Lysosomal Enzyme ◽  
Enzyme Activities ◽  
Lysosomal Enzymes ◽  
Culture Medium ◽  
Peritoneal Macrophages ◽  
Cellular Activity ◽  
Mouse Peritoneal Macrophages ◽  
Phospholipase A2 Activity

Resident mouse peritoneal macrophages have three phospholipase activities: a phospholipase A2 active at pH 4.5, a Ca2+-dependent phospholipase A2 active at pH 8.5 and a phosphatidylinositol-specific phospholipase C activity. When macrophages are exposed to zymosan in culture, the cellular activity of pH-4.5 phospholipase A2 is diminished in a manner dependent on zymosan concentration and time of exposure, whereas the cellular activities of pH-8.5 phospholipase A2 and phospholipase C remain unchanged. The depletion of pH-4.5 phospholipase A2 activity from the cell is paralleled by a quantitative recovery of this activity in the culture medium in a manner similar to the cellular depletion and extracellular recovery of two lysosomal enzymes. This release is specifically elicited by an inflammatory substance such as zymosan, since macrophages incubated with 6 micrometer latex spheres retain pH-4.5 phospholipase A2 activity and lysosomal enzyme activities intracellularly.

scholarly journals Fatty acid-mediated inhibition of IL-12 production by murine macrophages is independent of PPARγ

2004 ◽  
Vol 91 (5) ◽  
pp. 733-739 ◽  
Author(s):  
Meijuan Zhang ◽  
Kevin L. Fritsche
Keyword(s):  
Fatty Acid ◽  
Nuclear Receptors ◽  
Immune Cells ◽  
Inhibitory Effect ◽  
Peritoneal Macrophages ◽  
Immunomodulatory Activity ◽  
Pparγ Agonists ◽  
Mouse Peritoneal Macrophages

Our laboratory has reported that n-3 PUFA can reduce host resistance to Listeria infection, in part, by impairing in vivo IL-12 biosynthesis. Recently, PUFA were shown to be ligands for PPAR, a novel family of nuclear receptors with three isoforms: PPARα, PPARδ/β and PPARγ. PPARγ is expressed in immune cells, such as T cells and macrophages. Two PPARγ agonists, 15-deoxy-Δ12,14-prostaglandin (PG) J2 and rosiglitazone, have been shown to have immunomodulatory activity in vitro, including inhibiting IL-12 biosynthesis. We hypothesized that n-3 PUFA inhibit IL-12 production through activating PPARγ. We used thioglycolate-elicited mouse peritoneal macrophages to study the effect of various fatty acids and their oxidized metabolites on in vitro IL-12 production. Our present results demonstrate that both n-3 and n-6 PUFA can reduce in vitro IL-12 biosynthesis, though less potently than 15-deoxy-PGJ2 and rosiglitazone. GW9662, a PPARγ antagonist, reversed the inhibitory effect of rosiglitazone, but not that of PUFA. Our present findings suggest that fatty acid-mediated inhibition of IL-12 production is independent of PPARγ.

scholarly journals Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances.

1981 ◽  
Vol 90 (3) ◽  
pp. 656-664 ◽  
Author(s):  
S Ohkuma ◽  
B Poole
Keyword(s):  
Peritoneal Macrophages ◽  
Weak Base ◽  
Neutral Form ◽  
Osmotic Swelling ◽  
Cytoplasmic Vacuolation ◽  
Weak Bases ◽  
Protonated Forms ◽  
Basic Compounds ◽  
Mouse Peritoneal Macrophages ◽  
Basic Substances

With few exceptions, weakly basic compounds that are sufficiently lipophilic in their neutral forms and sufficiently hydrophilic in their protonated forms accumulate in lysosomes. When the concentration within the lysosomes becomes sufficiently high, osmotic swelling occurs. The cells than take on a vacuolated appearance. The concentrations at which different weak bases cause lysosomal vacuolation vary over almost three orders of magnitude. For any particular weak base, it is the concentration of the neutral form that determines the extent of uptake and the degree of vacuolation. Chloroquine is anomalous in that concentrations greater than approximately 30 microM cause less uptake and less vacuolation than do lower concentrations.

Sign in / Sign up

Export Citation Format

Share Document