Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ZYMOSAN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1987

The relationship between lysosomal enzyme release and protein phosphorylation in human monocytes stimulated by phorbol esters and opsonized zymosan.

Since it was established that phorbol esters bind to and activate protein kinase C, a proposed mechanism of action for these compounds has been the phosphorylation of specific protein substrates (Niedel, J. E., Kuhn, L. J., and Vandenbark, G. R. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 36-40; Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., and Nishizuka, Y. (1982) J. Biol. Chem. 257, 7847-7851). To better understand this proposed relationship, we investigated the ability of a series of phorbol esters to elicit lysosomal enzyme release (LER) and specific substrate phosphorylation in human monocytes. In this system, phorbol 12-myristate 13-acetate stimulated the secretion of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase in both a time- and concentration-dependent manner. Furthermore, the ability of a series of phorbol esters to stimulate LER was characterized and found to be in good agreement with the relative order of these compounds to stimulate the phosphorylation of four endogenous protein substrates. Phorbol ester-stimulated protein phosphorylation was examined in intact cell preparations and found to be concentration and structure-dependent. The phosphoproteins (pp) were designated pp28, pp55, pp61, and pp66 corresponding to their molecular masses in kilodaltons. These findings are consistent with the hypothesis that phorbol ester-mediated effects are the result of protein kinase C activation and subsequent protein phosphorylation. Finally, opsonized zymosan was found to elicit a concentration-dependent stimulation of N-acetyl-beta-D-glucosaminidase release similar in magnitude and time course to phorbol ester-stimulated LER. Opsonized zymosan also stimulated the phosphorylation of two phosphoproteins (pp61 and pp66) in a concentration-dependent manner. Specific phosphorylation of pp61 and pp66 by both secretagogues, phorbol 12-myristate 13-acetate and opsonized zymosan, suggests these two proteins may be key to the functional response of LER in human monocytes.

Acetylglucosaminidase↗
PubMed1985

Effect of divalent metal ions and pH upon the binding reactivity of human serum amyloid P component, a C-reactive protein homologue, for zymosan. Preferential reactivity in the presence of copper and acidic pH.

The serum amyloid P component (SAP) has been found to associate in vitro with a variety of polysaccharide and proteinaceous ligands including the yeast cell wall polysaccharide preparation, zymosan, in the presence of calcium at neutral pH. In the present study, we have investigated the role of copper and zinc and other divalent cations and acidic pH on the binding of SAP to zymosan. We report that binding occurs not only in the presence of calcium, but in the presence of copper, zinc, and cadmium as well. No binding occurs in the absence of added metal, or in the presence of barium, cobalt, magnesium, manganese, or nickel. 125I-SAP binding in the presence of metals is inhibited by presaturating the zymosan surface with unlabeled SAP. Whereas calcium-mediated binding decreases by more than 50% as the pH is lowered to 5, copper-mediated binding increases substantially at the more acidic pH values while zinc-mediated binding is essentially unchanged. These data indicate that, in addition to calcium at neutral pH, copper (and zinc) at neutral and particularly acidic pH values mediates SAP binding to polysaccharide ligands. This suggests that SAP may well be considered a copper- as well as a calcium-dependent protein under certain conditions and that this reactivity is favored under those conditions of lowered pH which may result from metabolic processes occurring at local sites of inflammation.

Amyloid↗
PubMed1984

Quantitative joint imaging using 67gallium citrate in a rabbit model of zymosan induced arthritis.

The intensity of synovitis induced by the intraarticular injection of 70 mg of zymosan into rabbit knee joints was assessed using the radiopharmaceutical 67gallium citrate (67Ga). Maximal uptake of 67Ga was observed 5 days after zymosan administration. The distribution of 67Ga in the intraarticular and paraarticular structures was quantitated and highest concentrations were found in the synovial membrane. The short term quantitative evaluation of zymosan induced arthritis is possible using scintigraphic technique.

Animals↗
PubMed1983

The origin of chemiluminescence produced by neutrophils stimulated by opsonized zymosan.

The luminol-dependent chemiluminescence (CL) of neutrophils phagocytosing zymosan is inhibited by superoxide dismutase (SOD), catalase, sodium benzoate, and 2,5-dimethyl furan. In the present report it is shown that inhibition by SOD and 2,5-dimethyl furan is diminished and removed, respectively, by the omission of glucose from the incubation medium. Zymosan-induced CL is also inhibited by inhibitors of arachidonic acid (AA) metabolism, including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin, and aspirin, by prostaglandins E1 and E2, theophylline, and dibutyryl cyclic AMP (cAMP), and by the addition of AA, sodium fluoride, and xanthine oxidase plus xanthine to the cell suspension. These findings lead us to postulate that the metabolism of AA via the lipoxygenase (and cyclooxygenase) pathway(s) is the source of CL observed in neutrophils after phagocytosis. Reactive oxygen species produced as a result of activation of NAD(P)H oxidase provide oxidizing agents for the oxidation of AA along these pathways. It is also suggested that elevated levels of cAMP induced by prostaglandins synthesized via the cyclooxygenase pathway may play a role in the regulation of the zymosan-induced CL response.

Arachidonic Acids↗
PubMed1980

Zymosan-induced experimental hypersensitivity pneumonitis in rabbits.

An experimental model of hypersensitivity pneumonitis is presented. New Zealand white rabbits, previously immunized against yeast-derived zymosan, reacted to intratracheal challenge developing extensive pneumonitis. The lesions healed in a few weeks. Control animals challenged with inert particulate material (latex beads) or suspending fluid (PBS-Mg++) did not show pulmonary inflammation. Nonimmunized rabbits developed only transient pneumonitis after zymosan challenge. This reaction was clearly different from that seen in the group of immunized animals. The model reveals that biologically active substances such as zymosan, which is able to activate the alternate pathway of complement and mononuclear phagocytes, requires an active immune state in order to cause significant tissue damage. Isolated exposure to this kind of substance may not be sufficient to cause lung disease.

Alveolitis, Extrinsic Allergic↗
PubMed1977

Hereditary C5 deficiency in man. III. Studies of hemostasis and platelet responses to zymosan.

Platelet-rich-plasma from two hemostatically normal individuals, genetically lacking the fifth component of complement (C5), failed to exhibit normal platelet aggregation, or serotonin release, in the presence of zymosan. This abnormality was found to reside in the C5D plasma rather than in the platelets as demonstrated by the inability of the deficient plasma to activate zymosan for the aggregation of washed normal platelets. The defect could be corrected by the addition of normal plasma, normal serlm, or highly purified human C5. A plasma abnormality similar to that found in the C5D individuals was also noted in plasmas deficient in C3, C6, and C7; whereas C8 plasma D behaved normally. These data suggest that this platelet reaction requires late acting C components, perhaps as the C567 complex, bound to the zymosan particles.

Blood Platelets↗
PubMed1998

Exogenous leukotriene B4 (LTB4) inhibits human neutrophil generation of LTB4 from endogenous arachidonic acid during opsonized zymosan phagocytosis.

The effect of exogenous leukotriene B4 (LTB4) on opsonized zymosan-stimulated human neutrophil formation of 5-lipoxygenase products and arachidonic acid release was directly assessed using reverse-phase HPLC/tandem mass spectrometric methods for quantitation. Stable isotopically labeled LTB4, [1,2-13C2]LTB4, caused a dose-dependent inhibition of LTB4 production in isolated human neutrophils with significant inhibition (60 +/- 7% of control levels) when 0.12 nM [13C2]LTB4 was present. Production of 5-hydroxy-6,8,11,14-eicosatetraenoic acid and release of free arachidonic acid were also dose-dependently inhibited by exogenous LTB4. Metabolites of LTB4, 20-hydroxy-LTB4 and 3(S)-hydroxy-LTB4, also significantly reduced LTB4 production to levels as low as 10 +/- 6% and 10 +/- 7% of control levels, respectively, when present exogenously at 10 nM. Exogenous 5-hydroxy-6,8,11,14-eicosatetraenoic acid at concentrations as high as 10 nM produced no significant reduction in LTB4 biosynthesis during zymosan-stimulated human neutrophil production of LTB4. The inhibitory effect of LTB4 could be partially reversed by the LTB4 receptor antagonist U 75302. Furthermore, an alternative stimulus, N-formyl-methionyl-leucyl-phenylalanine (100 nM), did not inhibit the production of LTB4 in opsonized zymosan-stimulated human neutrophils. These results suggest that activation of the LTB4 receptor on the human neutrophil during phagocytosis limits the ultimate biosynthesis of LTB4. This autocrine effect is opposite to that observed when neutrophils have much of the signal transduction pathways bypassed when stimulated with calcium ionophore A23187 or treated with exogenous free arachidonic acid.

Arachidonic Acid↗
PubMed1995

Effect of an enterally administered glutamine-rich protein on the catabolic response to a zymosan challenge in rats.

Glutamine is considered to be a conditionally essential amino acid during critical illness and has, therefore, been advocated to be included in nutritional support supplied in these situations. We investigated whether a diet containing a protein source rich in glutamine can restore depleted glutamine pools (plasma and muscle) and counteract muscle wasting, in a rat model of critical illness (intraperitoneal injection of zymosan). A glutamine-rich protein source was obtained by mixing a wheat protein hydrolysate (25% glutamine) with a whey protein isolate (to prevent essential amino acid deficiency). Feeding healthy control rats for 2 weeks with an adequate diet containing this protein source increased the two main glutamine pools (plasma and muscle). However, no effect was observed on the following zymosan-induced changes: 1) decreased glutamine and arginine concentrations (plasma and muscle), 2) wasting of muscle protein, and 3) decreased mitochondrial content in skeletal muscle. We conclude that a diet containing a glutamine-rich protein source can be used to increase plasma and muscle glutamine concentrations in healthy rats, but is of limited value to counteract wasting of skeletal muscle in zymosan-treated rats.

Journal Article↗
PubMed1998

Reduced cartilage proteoglycan loss during zymosan-induced gonarthritis in NOS2-deficient mice and in anti-interleukin-1-treated wild-type mice with unabated joint inflammation.

OBJECTIVE: To investigate the role of nitric oxide (NO) and interleukin-1 in (IL-1) joint inflammation and cartilage destruction during zymosan-induced gonarthritis (ZIA). METHODS: Monarticular arthritis was elicited by intraarticular injection of zymosan. The effect of NO deficiency on arthritis was studied in mice with genetically disrupted NOS2. The role of IL-1 was examined by treating wild-type mice with neutralizing anti-murine IL-1(alpha+beta) antibodies. Joint swelling was measured externally by the increased uptake of circulating 99mtechnetium pertechnetate. Proteoglycan (PG) synthesis was assessed using 35S-sulfate incorporation into patellae ex vivo. Histology evaluated exudation and infiltration of leukocytes and the extent of cartilage destruction. RESULTS: The proinflammatory mediators NO, IL-1, and IL-6 were released by the articular tissues during the first hours of inflammation. Interestingly, anti-IL-1 treatment moderately reduced, and NOS2 deficiency moderately enhanced, joint swelling. However, the influx of neutrophils into the joint occurred independently of IL-1 and NOS2 activities. In the first week of inflammation, chondrocyte PG synthesis was significantly suppressed and chondrocytes became unresponsive to their essential anabolic factor, insulin-like growth factor 1 (IGF-1). Anti-IL-1 treatment or NOS2 deficiency prevented the inhibition of PG synthesis, and the chondrocytes remained IGF-1 responsive. Intraarticular injections of IL-1alpha into NOS2-deficient mice did not affect PG synthesis, thus proving that NO mediated this IL-1 effect in vivo. Furthermore, histology showed that cartilage PG loss was markedly ameliorated in NOS2-deficient and anti-IL-1-treated mice. Intermediate cartilage pathology was found in mice that were heterozygous for disrupted NOS2. CONCLUSION: IL-1 and NO play a minor role in edema and neutrophil influx, but a major role in cartilage destruction of ZIA. In this model of murine arthritis, cartilage destruction was, for the most part, caused by pronounced suppression of PG synthesis and IGF-1 unresponsiveness of the chondrocytes, which were induced by de novo-synthesized IL-1 and were mediated by NOS2 activation.

Animals↗
PubMedDate not supplied

Zymosan-induced arthritis: a model of chronic proliferative arthritis following activation of the alternative pathway of complement.

Zymosan particles, which are able to activate complement by the alternative pathway and to induce enzyme secretion from macrophages, were injected into knee joints of mice. After various time intervals, synovia were assessed histologically for various markers of inflammation. Within 7 days after intraarticular injection of zymosan, a chronic inflammatory arthritis with mononuclear cell infiltration, synovial hypertrophy and pannus formation was observed. Latex particles, which do not activate complement or macrophages, produced only mild, transient inflammatory reactions.

Animals↗
PubMed1995

Role of interleukin-1, tumor necrosis factor alpha, and interleukin-6 in cartilage proteoglycan metabolism and destruction. Effect of in situ blocking in murine antigen- and zymosan-induced arthritis.

OBJECTIVE: To determine the involvement of interleukin-1 (IL-1), tumor necrosis factor (TNF), and IL-6 in the cartilage pathology of murine antigen-induced arthritis (AIA) and zymosan-induced arthritis (ZIA). METHODS: Arthritis was induced by intraarticular injection of zymosan in naive mice or by subcutaneous injection of methylated bovine serum albumin in sensitized animals. Mini-osmotic pumps releasing human recombinant IL-1 receptor antagonist (IL-1ra) protein were implanted intraperitoneally 2 days before arthritis induction, and neutralizing antibodies directed against murine IL-1 alpha, IL-1 beta, TNF alpha, or IL-6 were administered 1 day before. Proteoglycan (PG) synthesis and degradation were assessed in patellar cartilage. RESULTS: Murine IL-1 alpha and IL-1 beta injected intraarticularly at doses of 0.1-100 ng suppressed chondrocyte PG synthesis. The highest dose of TNF tested (100 ng) decreased PG synthesis marginally. In contrast, the maximum dose of IL-6 (1 microgram) stimulated PG synthesis 2 days after injection. Treatment of AIA with neutralizing monoclonal antibodies against either TNF alpha or IL-6 did not reduce either the PG degradation or the suppression of its synthesis. However, treatment with anti-IL-1 (alpha + beta) polyclonal antibodies totally prevented PG suppression, although the initial breakdown of PG was unaffected. This effect was confirmed when IL-1ra was administered in high doses. Moreover, treatment of ZIA with anti-IL-1 (alpha + beta), but not with anti-TNF, resulted in normal PG synthesis, confirming the key role played by IL-1 in the inhibition of PG synthesis. Treatment of AIA with anti-IL-1 did not affect inflammation during the acute phase, but a significant reduction of ongoing inflammation was noted at day 7, and there was a marked reduction in the loss of cartilage PG. CONCLUSION: The suppression of PG synthesis in both ZIA and AIA in mice is due to the combined local action of IL-1 (alpha + beta), and neither IL-6 nor TNF is involved. Moreover, the normalization of PG synthesis brought about by blocking of IL-1 ameliorates the cartilage damage associated with AIA.

Animals↗
PubMedDate not supplied

Magnesium-dependent induction of phagocytosis-associated chemiluminescence of adherent human polymorphonuclear leukocytes by non-opsonized zymosan.

A severe dysfunction in the cellular response of human polymorphonuclear leukocytes (PMNL) to non-opsonized zymosan was observed under a deficiency of extracellular Mg2+. The phagocytosis-association native (luminol-independent) luminescence (NL), as well as luminol-dependent luminescence (LDL) (detected simultaneously and discriminated by spectral methods), was strongly inhibited. Apart from a general decrease of total light production, a Mg2+-concentration-dependent delay of the maximum of NL and LDL was observed. A disorder in recruitment of activated membrane-bound NADPH-oxidase of PMNL is suggested. The presence of extracellular Ca2+ did not compensate for the Mg2+ deficit. In the presence of Mg2+ only a slight Ca2+-dependent reduction of NL was obtained, but Ca2+ seemed to selectively promote LDL. This may indicate a positive influence of Ca2+ on the myeloperoxidase release from the cells. Experiments with the metalions-chelating agents EDTA and EGTA, which complex Mg2+ to differing extents, confirmed the important role of Mg2+ in PMNL-activation by non-opsonized zymosan.

Calcium↗
PubMedDate not supplied

Importance of local proliferation in the expanding Kupffer cell population of rat liver after zymosan stimulation and partial hepatectomy.

Partial hepatectomy and a single intravenous injection of zymosan were used to provoke expansion of the Kupffer cell population in rat liver. The number of Kupffer cells per microscopic field increased exponentially for 4 to 5 days after either stimulation. During this exponential growth phase, high mitotic activity of Kupffer cells was observed. The rate of mitosis, based on counts of cells arrested in metaphase by vinblastin, was compared with the increase in total cell population. During the first 3 days after partial hepatectomy, local proliferation was sufficient to explain the increase in population since the mean potential doubling time was 1.3 days compared to an observed doubling time of 3.7 days. During the first 3 days after zymosan stimulation, observed doubling time was 4.3 days compared with the mean potential doubling time of 5.2 days which led to the conclusion that growth is largely due to local proliferation of Kupffer cells. In both experimental situations, extrahepatic recruitment of "resident-type" macrophages was required during the last 2 days of the growth phase, since mitotic activity became too low to explain the observed growth. Proliferating Kupffer cells had characteristics of mature resident macrophages and were, therefore, considered to be different from elicited "exudate-type" cells, such as monocytes.

Animals↗
PubMed1987

Zymosan-stimulated production of phosphatidic acid by macrophages: relationship to release of superoxide anion and inhibition by agents that increase intracellular cyclic AMP.

Murine peritoneal macrophages (m phi) respond to unopsonized zymosan with the production of superoxide anion (O2-). We investigated the involvement of phospholipid turnover in the transduction mechanism for this phenomenon. Zymosan-stimulated m phi produced increased amounts of phosphatidic acid (PA); the increase was first detected at 1.5 min and continued for 10 min of incubation. Production of O2- was not detected until between 2 to 4 min after stimulation, and continued to increase through 60 min. Inhibition experiments suggested that these two processes were linked. Theophylline (theo)/dibutyrylcyclic AMP (dbcAMP) and theo/prostaglandin E2 (PGE2) inhibited O2- production at every time point (79% and 80% inhibition, respectively, at 4 min). Corresponding inhibition of PA production was also achieved at every time point (85% by theo/dbcAMP; 67% by theo/PGE2 at 4 min). These results are compatible with a role for phospholipid remodeling in the transduction process associated with the respiratory burst. Results suggest that the phospholipid species could be phosphatidylcholine (PC) as well as phosphatidylinositol (PI).

Animals↗
PubMed1998

Endogenous monocyte chemoattractant protein-1 recruits monocytes in the zymosan peritonitis model.

The role of monocyte chemoattractant protein-1 (MCP-1) in the recruitment of blood-derived monocytes in a model of zymosan peritoneal inflammation was investigated. After zymosan injection (1 mg) a rapid influx of polymorphonuclear leukocytes (PMN) and monocytes into the peritoneal cavity associated with mouse MCP-1 (JE) gene activation and protein secretion in the exudates occurred. MCP-1 production (maximal at 4 h) preceded the accumulation of monocytes (F4/80-positive cells, maximally recovered between 16 and 24 h). Treatment of mice with a single injection of anti-mouse MCP-1 antibody inhibited 16-h monocyte accumulation by approximately 40%, however, a significant decrease in the number of PMN was also measured. Finally, intraperitoneal injection of murine recombinant MCP-1 (1 microg) produced a selective accumulation of monocytes (F4/80-positive cells) into the peritoneal cavity. In conclusion, we show the novel existence of a strict relationship between MCP-1 production and leukocyte accumulation in this model of acute inflammation.

Acute Disease↗
PubMed1997

Quantitation of 5-lipoxygenase products by electrospray mass spectrometry: effect of ethanol on zymosan-stimulated production of 5-lipoxygenase products by human neutrophils.

A reverse-phase-HPLC/tandem mass spectrometric method (LC/MS/MS) was developed for the quantitation of leukotriene B4 (LTB4), the 5-lipoxygenase product, 5-hydroxyeicosatetraenoic acid (5-HETE), as well as the omega-oxidation metabolites of LTB4, 20-hydroxy-LTB4, and 20-carboxy-LTB4. Electrospray-generated carboxylate anions were collisionally activated and decomposed to specific and abundant product ions and multiple reaction monitoring was used to analyze LTB4 (m/z 335-->195), 20-hydroxy-LTB4 (m/z 351-->195), 20-carboxy-LTB4 (m/z 365-->195), and 5-HETE (m/z 319-->115). A linear correlation was observed in comparison of results obtained from quantitation by LC/MS/MS with quantitation by gas chromatography/MS of the pentafluorobenzyl ester/trimethylsilyl ether derivative of LTB4 produced during opsonized zymosan stimulation of human neutrophils. Detection limits at the low picogram level were obtained for all metabolites. This method was applied to the quantitation of 5-lipoxygenase products produced from zymosan-stimulated human neutrophils in the presence of ethanol. At physiologically relevant concentrations of ethanol, production of all 5-lipoxygenase products generated by stimulated neutrophils was markedly attenuated.

Arachidonate 5-Lipoxygenase↗
PubMed1998

Hypoxia-reoxygenation potentiates zymosan activated plasma-induced endothelial injury.

The pathophysiology of ischemia-reperfusion injury and the role played by the interaction of plasma proteins, including complement, with reperfused endothelium remains incompletely understood. Venular endothelial changes due to hypoxia followed by reoxygenation (H-R) are vital because venules are the primary site of fluid accumulation and polymorphonuclear leukocyte deposition due to inflammation. This investigation focused on whether H-R potentiates the response to permeability inducing agents found in activated plasma. Activated complement was studied by using zymosan activated plasma (ZAP). Permeability changes were assessed by quantitating rate of clearance of albumin across the monolayers. H-R alone did not change permeability relative to the normoxic condition. ZAP at 2% in normoxic cells increased albumin clearance from 2 +/- 0.2 to 9 +/- 1. 0 microL/h, which increased significantly to 13.5 +/- 2.0 microL/h when given to hypoxia-reoxygenation challenged monolayers. The permeability response to ZAP was dose related and not present with heat inactivated ZAP. ZAP at 2% altered the structure of the cytoskeleton of the human umbilical vein endothelial cells (HUVEC). However, addition of monoclonal anti-complement antibodies or addition of soluble complement receptor-1 did not attenuate ZAP-induced HUVEC permeability. Addition of zymosan-activated serum did not alter the permeability and addition of heparin inhibited the ZAP-induced changes in permeability, suggesting that these changes were mediated via thrombin and not complement. The increase in monolayer permeability due to ZAP was prevented by increasing intracellular adenosine-3',5'-cyclic monophosphate. These findings suggest that HUVEC monolayers challenged with H-R are more susceptible to increases in permeability induced by activated plasma components.

Actins↗
PubMed1989

Activation and migration of leukocytes and vascular leakage induced by serum-opsonized zymosan particles in hamster cheek pouch.

The effect of topically applied serum-opsonized zymosan (SOZ) and zymosan-activated serum (ZAS) was studied in the hamster cheek pouch. Our data suggest that early vascular leakage, evaluated by intravital fluorescence microscopy after injection of FITC-dextran, and accumulation of polymorphonuclear granulocytes (PMNGs), quantitated in fixed whole tissue specimens, induced by ZAS and SOZ were caused by complement activation, whereas the late leakages (greater than 20 min after SOZ application) was PMNG-dependent. Inhibition of prostaglandin and leukotriene synthesis by indomethacin, nordihydroguaiaretic acid (NDGA), and BW755C influence early and late vascular leakage as well as accumulation of PMNGs. These drugs also inhibited the activation of hamster PMNGs in vitro, as evaluated by chemiluminescence, in a dose-dependent manner. (-)-Terbutaline, an adrenergic beta agonist, decreased vascular leakage but had no effect on PMNG activation and accumulation.

Animals↗