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 973 records · Page 54Linked to original sources
PubMed2001

A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats.

Immune activation near healthy peripheral nerves may have a greater role in creating pathological pain than previously recognized. We have developed a new model of sciatic inflammatory neuritis to assess how such immune activation may influence somatosensory processing. The present series of experiments reveal that zymosan (yeast cell walls) acutely injected around the sciatic nerve of awake unrestrained rats rapidly (within 3h) produces low threshold mechanical allodynia in the absence of thermal hyperalgesia. Low (4 microg) doses of zymosan produce both territorial and extra-territorial allodynia restricted to the ipsilateral hindpaw. Higher (40-400 microg) doses of zymosan again produce both territorial and extra-territorial allodynia. However, allodynia is now expressed both in the ipsilateral as well as contralateral hindpaws. Several lines of evidence are provided that the appearance of this contralateral ('mirror') allodynia reflects local actions of zymosan on the sciatic nerve rather than spread of this immune activator to the general circulation. Since many clinical neuropathies result from inflammation/infection of peripheral nerves rather than frank physical trauma, understanding how immune activation alters pain processing may suggest novel approaches to pain control.

Acute Disease↗
PubMed2002

Gamma-tocopherol supplementation inhibits protein nitration and ascorbate oxidation in rats with inflammation.

Gamma-tocopherol (gammaT) complements alpha-tocopherol (alphaT) by trapping reactive nitrogen oxides to form a stable adduct, 5-nitro-gammaT [Christen et al., PNAS 94:3217-3222; 1997]. This observation led to the current investigation in which we studied the effects of gammaT supplementation on plasma and tissue vitamin C, vitamin E, and protein nitration before and after zymosan-induced acute peritonitis. Male Fischer 344 rats were fed for 4 weeks with either a normal chow diet with basal 32 mg alphaT/kg, or the same diet supplemented with approximately 90 mg d-gammaT/kg. Supplementation resulted in significantly higher levels of gammaT in plasma, liver, and kidney of control animals without affecting alphaT, total alphaT+gammaT or vitamin C. Intraperitoneal injection of zymosan caused a marked increase in 3-nitrotyrosine and a profound decline in vitamin C in all tissues examined. Supplementation with gammaT significantly inhibited protein nitration and ascorbate oxidation in the kidney, as indicated by the 29% and 56% reduction of kidney 3-nitrotyrosine and dehydroascorbate, respectively. Supplementation significantly attenuated inflammation-induced loss of vitamin C in the plasma (38%) and kidney (20%). Zymosan-treated animals had significantly higher plasma and tissue gammaT than nontreated pair-fed controls, and the elevation of gammaT was strongly accentuated by the supplementation. In contrast, alphaT did not significantly change in response to zymosan treatment. In untreated control animals, gammaT supplementation lowered basal levels of 3-nitrotyrosine in the kidney and buffered the starvation-induced changes in vitamin C in all tissues examined. Our study provides the first in vivo evidence that in rats with high basal amounts of alphaT, a moderate gammaT supplementation attenuates inflammation-mediated damage, and spares vitamin C during starvation-induced stress without affecting alphaT.

Animals↗
PubMed2002

Regulation of phospholipase C-gamma 2 via phosphatidylinositol 3-kinase in macrophages.

Phospholipase C-gamma (PLC-gamma) isoforms are thought to be activated by both tyrosine phosphorylation and phosphatidylinositol 3,4,5 trisphosphate (PtdIns 3,4,5 P(3)), the product of phosphatidylinositol 3-kinase (PtdIns 3-kinase). In this study, we show that stimulation of mouse macrophages with either zymosan beads or bacteria (Prevotella intermedia) induced tyrosine phosphorylation of PLC-gamma 2. Zymosan stimulation also induced translocation to membrane and cytoskeleton fractions, which was inhibited by the PtdIns 3-kinase inhibitors wortmannin and LY 294002. However, the tyrosine phosphorylation of PLC-gamma 2 induced by zymosan was not affected by the inhibitors wortmannin and LY 294002. In contrast to zymosan and bacteria, PLC-gamma 2 was not phosphorylated by stimulation with lipopolysaccharide (LPS), phorbol ester or calcium ionophore. Moreover, the PLC-gamma 1 isoform was not detected in mouse macrophages. These data indicate that PtdIns 3-kinase is critical for the translocation but not for the tyrosine phosphorylation of PLC-gamma 2 in mouse macrophages and that the latter may be insufficient for enzyme activation.

Androstadienes↗
PubMed1994

Role of activated macrophages in augmentation of endotoxin hepatotoxicity.

In this study, to clarify the role of activated macrophages in the augmentation of endotoxin hepatoxicity, rats were pretreated with zymosan, an activator of macrophages, before the induction of endotoxin hepatotoxicity, and some were given pentoxifylline, an inhibitor of tumour necrosis factor production. The intravenous injection of zymosan induced many granulomas composed of macrophages in the lungs and the liver, while the intraperitoneal injection caused granulomas in the greater omentum. Endotoxin hepatotoxicity. as shown by focal and random hepatocellular coagulative necrosis and elevation of serum transaminase activities, was more intense in the rats pretreated with zymosan than in those which were not injected with zymosan. This augmented endotoxin hepatotoxicity was significantly inhibited by pentoxifylline treatment. These findings indicate that endotoxin hepatotoxicity may be augmented in the presence of activated macrophages which produce chemical mediators, particularly tumour necrosis factor.

Animals↗
PubMed1989

Biosynthesis of paf-acether. Paf-acether but not leukotriene C4 production is impaired in cultured macrophages.

After adherence for 24 or 48 h mouse peritoneal macrophages, upon a zymosan challenge, synthesized 114 +/- 55 and 82 +/- 31 pmol of paf-acether (paf)/mg of protein respectively, as compared with 513 +/- 195 pmol of paf/mg of protein in 2 h-adherent macrophages (means +/- S.D., n = 10). By contrast, 24 h- and 48 h-adherent macrophages exposed to zymosan produced more leukotriene C4 (2.7 +/- 1.1 and 1.4 +/- 0.2 nmol/mg of protein respectively, n = 5) than did 2 h-adherent macrophages (0.5 +/- 0.2 nmol/mg of protein, n = 5). Paf production was not altered when 2 h- and 24 h-adherent cells were cultured and/or stimulated in the presence of 5 microM-indomethacin, 10 microM-nordihydroguaiaretic acid or 100 microM-BW755C as compared with untreated cells. These results indirectly exclude the regulation of paf production by arachidonic acid metabolites. We investigated the efficiency of the enzymic steps which govern paf synthesis. We showed that the anabolic process was not impaired since (1) the amounts of alkylacylglycerophosphocholine and lyso-paf were similar in 2 h-, 24 h- and 48 h-adherent macrophages; (2) adding synthetic lyso-paf or acetyl-CoA to intact cells did not increase paf production in zymosan-stimulated 24 h- and 48 h-adherent macrophages; (3) the basal level of acetyltransferase was comparable in 2 h-, 24 h- and 48 h-adherent macrophages and in all cases was increased by 2-3 times upon zymosan challenge. We also showed that impaired paf production in 24 h- and 48 h-cultured macrophages was not due to the nature of the stimulus used to induce its synthesis.

Acetyltransferases↗
PubMed1996

Radical scavenger activity of three flavonoid metabolites studied by inhibition of chemiluminescence in human PMNs.

3,4-Dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)-propionic acid, metabolites which arise from quercetin glycosides, respectively, from flavones and probably from procyanidins by the human intestinal microflora, have been tested for their effects on oxygen radical production by human PMNs stimulated with FMLP or opsonized zymosan. Oxygen radicals were detected by luminol-augmented chemiluminescence measurements. Furthermore free radical scavenging activity of these metabolites was investigated in a cell-free system in which oxygen radicals were generated by horseradish peroxidase with H2O2 as substrate. 3,4-Dihydroxyphenylacetic acid reduced considerably chemiluminescence in PMNs in an amount which was much more pronounced than those of the other two metabolites. Concentrations of 1 mumol/l showed an inhibition by 84% with FMLP as stimulant and by 15% with opsonized zymosan, indicating that different signal transduction pathways are influenced in PMNs. Using the same conditions the unmetabolized quercetin showed an inhibition of chemiluminescence by 74% (FMLP), resp. 20% (opsonized zymosan). In the cell free system 3,4-dihydroxyphenylacetic acid suppressed much more effectively chemiluminescence than 3-hydroxyphenylacetic acid. In contrast, 3-(4-hydroxyphenyl)-propionic acid led to an increase of chemiluminescence generated in the cell-free system (FMLP and zymosan), i.e. by 30% by 25%, at the highest concentration of 4 mumol/l. In conclusion, flavonoid metabolites differ in their effects on free radical production of PMNs and their radical scavenging potencies.

Flavonoids↗
PubMed1998

The role of calcium and phosphorylation of cytosolic phospholipase A2 in regulating arachidonic acid release in macrophages.

Arachidonic acid release is induced in macrophages with diverse agonists including calcium ionophores, phorbol myristate acetate (PMA), okadaic acid, and the phagocytic particle, zymosan, and correlates with activation of cytosolic phospholipase A2 (cPLA2). The role of calcium and phosphorylation of cPLA2 in regulating arachidonic acid release was investigated. Zymosan induced a rapid and transient increase in [Ca2+]i. This in itself is not sufficient to induce arachidonic acid release since ATP and platelet activating factor (PAF), agonists that induce transient calcium mobilization in macrophages, induced little arachidonic acid release. Unlike zymosan, which is a strong activator of mitogen-activated protein kinase (MAPK), ATP and PAF were weak MAPK activators and induced only a partial and transient increase in cPLA2 phosphorylation (gel shift). However, ATP or PAF together with colony stimulating factor-1 (CSF-1) synergistically stimulated arachidonic acid release. CSF-1 is a strong MAPK activator that induces a rapid and complete cPLA2 gel shift but not calcium mobilization or arachidonic acid release. Arachidonic acid release was more rapid in response to CSF-1 plus ATP or PAF than zymosan and correlated with the time course of the cPLA2 gel shift. Although low concentrations of ionomycin induced a lower magnitude of calcium mobilization than ATP, the response was more sustained resulting in arachidonic acid release. A23187 and ionomycin induced weak MAPK activation, and a partial and transient cPLA2 gel shift. The MAPK kinase inhibitor, PD 98059 suppressed A23187-induced MAPK activation and cPLA2 gel shift but had little effect on arachidonic acid release. These results indicate that in macrophages a transient increase in [Ca2+]i and sustained phosphorylation of cPLA2 can act together to promote arachidonic acid release but neither alone is sufficient. A sustained increase in calcium is sufficient for inducing arachidonic acid release. However, PMA and okadaic acid induce arachidonic acid release without increasing [Ca2+]i, although resting levels of calcium are required, suggesting alternative mechanisms of regulation.

Animals↗
PubMed1974

Potassium and amino acid transport in human leukocytes exposed to phagocytic stimuli.

Influxes of potassium and amino acids were measured in suspensions of human polymorphonuclear leukocytes (PMNs) under resting conditions and after various phagocytic stimuli. Both ouabain-sensitive (or pump) and ouabain-insensitive (or leak) influxes of K were determined. In 5 mM external K, mean total K influx was 0.69 nmol/10(6) cells x min, of which 52% was ouabain-sensitive. Ouabain binding was irreversible, and, as in erythrocytes, was inhibited by K. At external concentrations of 0.1 mM, influxes of lysine and leucine were entirely carrier-mediated, with means of 0.021 nmol/10(6) cells x min, and 0.019 nmol/10(6) cells x min, respectively. After incubation of PMNs with zymosan or latex particles, the K pump was reduced more than 60%, whereas amino acid influxes were inhibited only by 30%. PMNs were also exposed to cytochalasin B before challenge by particles: the drug prevented phagocytosis but not surface binding of zymosan, nor did it influence transport of K or amino acids. After pretreatment of PMNs with cytochalasin B, interaction of zymosan with their surface resulted in the same degree of inhibition of influxes of K and amino acids as when the cells were permitted to phagocytose the particles. In contrast, exposure of PMN to latex particles, which do not bind to cytochalasin B-treated cells, after pretreatment of cells with cytochalasin B did not result in inhibition of influxes. Treatment of cells with colchicine had no effect on either membrane transport or its inhibition after exposure to various phagocytic stimuli. These results indicate that the surface membranes of PMNs are functionally heterogeneous with respect to the association of transport sites for the different solutes. Moreover, loss of specific membrane functions from phagocytosing cells may result from the surface-at-tachment phase of particle-cell interactions, since the interactions of zymosan particles with PMNs in the absence of phagocytosis also inhibited transport of solutes.

Amino Acids↗
PubMed1984

Human pulmonary macrophage-derived mucus secretagogue.

Human pulmonary macrophages (PM) obtained from surgically removed human lung tissue released a factor after exposure to activated zymosan that caused cultured human airways to release increased amounts of radiolabeled mucous glycoproteins. The factor was released maximally after 4-8 h of zymosan exposure and caused a dose-related increase in glycoprotein release; it was termed macrophage-derived mucus secretagogue (MMS). MMS release was produced in a dose-dependent fashion by activated but not by nonactivated zymosan. The activation of zymosan was C3 dependent, and C3b-coated Sepharose was also an effective stimulant. The data suggested that cell surface activation of the PM was a sufficient stimulus to cause MMS release and that both C3-dependent activation as well as Fc receptor activation were effective. The synthesis of MMS was sensitive to cycloheximide, and no active MMS was detectable intracellularly. To determine if MMS might be one of the oxidative derivatives of arachidonic acid, PM were incubated with cyclooxygenase and lipoxygenase inhibitors before activation. These maneuvers did not influence MMS generation. MMS-rich supernatants were then extracted into organic solvents or exposed to lipophilic resin; in both cases, MMS remained in the aqueous phase. Thus, MMS is not a derivative of arachidonic acid. Sequential fractionation of MMS on ultramembrane and gel filtration followed by isoelectric focusing and gel filtration indicated that MMS is a small (approximately 2000 daltons), acidic (pI, 5.15) molecule. Therefore, surface activation of human PM results in the synthesis and release of a small acidic molecule that causes airway mucous glands to secrete increased quantities of mucous glycoproteins.

Animals↗
PubMed1987

Modification of luminol-dependent chemiluminescence reactivity of peripheral blood leukocytes from patients with lymphoreticular tumor, solid cancer, or healthy blood donors by interferon-alpha.

The effect of interferon-alpha (rIFN-alpha 2) on modulating the luminol-dependent chemiluminescence (CL) response evoked by Zymosan or phorbol myristate acetate (PMA) has been studied in heparinized whole blood as well as isolated peripheral blood leukocytes derived from cancer patients and healthy blood donors. The cancer patients, diagnosed with chronic leukemia or lymphoma or solid cancer, were under rIFN-alpha 2 therapy. The CL emission to both Zymosan or PMA was enhanced in the whole blood of the patient's group in comparison to whole blood of healthy blood donors. CL reactivity induced in Dextran-sedimented leukocytes derived from neoplasia patients and healthy blood donors did not differ in the two groups. CL reactivity to Zymosan or PMA could be potentiated when whole blood samples or isolated leukocytes of patients or healthy blood donors were incubated in vitro with rIFN-alpha 2 in the range of 0.001-1000 U/ml prior to addition of CL-stimulating agents. rIFN-alpha 2 itself without adding further agents did not stimulate CL reactivity. Therefore, enhanced CL reactivity to PMA or Zymosan observed in the whole blood of the patients' population appears to be due to the presence of interferon in serum blood components as a consequence of IFN-infusion rather than to other symptoms or treatments of the neoplastic diseases, since the relative CL enhancement in patients is abrogated when isolated blood leukocytes are used for CL assay.

Adult↗
PubMed1980

Adherence of polymorphonuclear leukocytes to nylon: modulation by prostacyclin (PGI2), corticosteroids, and complement activation.

Effects of in vitro addition of prostacyclin (PGI2), hydrocortisone, and zymosan to plasma on adherence of polymorphonuclear leukocytes (PMNLs) to nylon were investigated. PGI2, in nanogram concentrations, and hydrocortisone, in high concentrations, inhibited base-line adherence of PMNLs; zymosan-treated plasma augmented retention of PMNLs by nylon columns. Incubation of plasma with antiserum to C5, hydrocortisone, or PGI2 blocked zymosan-mediated effects. Prostaglandins (PGD2, PGE1, and PGF2 alpha) when added in votro did not alter base-line adherence. PMNLs obtained 4 hr after administration of oral prednisone to volunteers were partially resistant to effects of zymosan-activated plasma.

Adrenal Cortex Hormones↗
PubMed1987

Formation of mixed disulfide of cystatin-beta in cultured macrophages treated with various oxidants.

Macrophage cell cultures were treated with menadione, zymosan, or phorbol myristate acetate (PMA), and changes in productions of superoxide anion and hydroperoxide, and in glutathione oxidation and S-thiolation of cystatin-beta (formation of a mixed disulfide of cystatin-beta and glutathione) were examined. All three compounds promoted production of superoxide anion and hydroperoxide, but only menadione caused extensive oxidation of glutathione. Menadione caused S-thiolation of cystatin-beta in a dose-dependent fashion, but the other two compounds did not. Removal of menadione promptly reduced the oxidation of glutathione and S-thiolation of cystatin-beta induced by menadione. Inhibition of catalase by aminotriazol caused slight increase in the GSSG content in both menadione- and zymosan-treated cells, but not in S-thiolation of cystatin-beta in zymosan-treated cells. None of the three compounds influenced appreciably the activity of glutathione peroxidase, glutathione reductase, or superoxide dismutase in cultured cells. These results indicate that S-thiolation of cystatin-beta occurs in cells in response to oxidative challenge by menadione but not by zymosan or by the tumor promoter PMA. Dethiolation of cystatin-beta by purified thiol transferase and protein disulfide isomerase in the presence of different concentrations of GSH was examined in vitro. Both enzymes catalyzed dethiolation of cystatin-beta at a much lower level of GSH than that required for the non-enzymatic reaction, suggesting the importance of enzymatic catalysis of S-thiolation and dethiolation of cystatin-beta in cells.

Animals↗
PubMed1993

Changes in myocardial blood flow rates during hyperdynamic sepsis with induced changes in arterial perfusing pressures and metabolic need.

OBJECTIVE: To determine whether hyperdynamic sepsis is associated with dysregulation in the control of myocardial blood flow rates unrelated to hypotension or the use of anesthetic agents. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Fifteen mature male sheep (34 to 61 kg). INTERVENTIONS: Data were recorded in study subjects before and after the induction of sepsis following cecal ligation and perforation. Data were then recorded during: a) an infusion of prostaglandin E1 (PGE1), which decreased mean arterial perfusing pressure; and b) an infusion of zymosan-activated plasma, which increased mean pulmonary arterial pressures. MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow rates were measured by the radiolabeled microsphere technique and cardiac index was measured by the thermodilution technique. Cardiac index (change delta) postcecal ligation and perforation minus baseline (+2.3 +/- 1.0 L/min/m2; p < .01) was increased in the septic study. Blood flow rate to the left ventricle was simultaneously increased, and was not further affected when the PGE1 infusion decreased the mean arterial perfusing pressures (-19 +/- 4%). During the infusion of zymosan-activated plasma, mean pulmonary arterial pressures increased (50 +/- 30%) and right ventricular blood flow was increased (zymosan minus postcecal ligation and perforation study: delta 17.8 +/- 50 mL/100 g/min; p < .01). CONCLUSIONS: In this model of hyperdynamic sepsis, increases in blood flow to both the left and right ventricles were positively coupled to changes in respective ventricular work. From the interventional PGE1 and zymosan-activated plasma infusion studies, we found no evidence to support previous suggestions that the regulation of myocardial blood flow rates according to changes in perfusing pressure and/or metabolic oxygen need is significantly altered during hyperdynamic sepsis.

Alprostadil↗
PubMed1996

Alterations in endothelial barrier permeability in multiple organs during overactivation of macrophages in rats.

Macrophage hyperactivity has been suggested to play an important role in septic complications and the development of multiple organ failure. Intraperitoneal administration of macrophage stimulants, e.g., zymosan, induce a systemic inflammatory response, with concomitant gut origin sepsis, and organ dysfunction. However, little is known about alterations in endothelial permeability during macrophage hyperactivation. In the present study, the effect of macrophage hyperactivation on endothelial permeability, assessed by 125I-labeled HSA and 51Cr-labeled EDTA, and the difference between cytolytic and noncytolytic inflammatory macrophages induced by i.p. injection of .25 or .50 mg/g of zymosan, concanavalin A (Con A) or thioglycollate medium (TM) diluted in 4 mL of paraffin, as well as the potential relationship with the doses used, were evaluated in the rat. Overactivation of cytolytic inflammatory macrophages induced a pronounced alteration in endothelial barrier permeability, characterized by a decrease in whole body plasma volume and an increase in whole body interstitial fluid volume, while overactivation of noncytolytic inflammatory macrophages only induced leakage of proteins and plasma to several of the organs studied. Macrophage activators, like zymosan, Con A and TM, exhibited varying effects on endothelial permeability related to the dose used. The results in the present study imply that overactivation of cytolytic inflammatory macrophages may play an important role in endothelial barrier injury and that zymosan possesses a more potent effect as compared to Con A when administered at the same dose.

Animals↗
PubMed2003

Platelet-activating factor acetylhydrolase inhibits alveolar macrophage activation in vivo.

Platelet-activating factor (PAF) is an important proinflammatory mediator of septic shock. PAF is produced by activated macrophages and acts to perpetuate the response to endotoxin. PAF is metabolized by an endogenous PAF-acetylhydrolase (PAF-AH). Low circulating levels of PAF-AH have been associated with the development of postinjury multiple organ failure. We have previously shown that PAF-AH significantly inhibits macrophage activation by lipopolysaccharide (LPS) in vitro. The purpose of these studies was to determine whether this effect would translate to an in vivo model of remote lung injury. Wistar rats were administered a single intravenous dose of PAF-AH (5 mg/kg) or its carrier solution simultaneous with the induction of zymosan peritonitis. After 24 h, alveolar macrophages were obtained by bronchoalveolar lavage and stimulated in vitro with LPS (1 microg/mL). Supernatants were collected at 18 h for cytokine production and cellular and nuclear protein extractions were performed at 30 and 60 min to assess the activation of p38 and extracellular signal-regulated kinase (ERK) 1/2 kinases and the nuclear translocation of nuclear factor (NF)-kappaB. Administration of PAF-AH significantly inhibited LPS-induced tumor necrosis factor alpha and interleukin-1beta production by alveolar macrophages from zymosan-treated animals. This functional inhibition was associated with inhibition of ERK 1/2 kinase and NF-kappaB activation but not p38 kinase activation. Interleukin 6 production was depressed in the macrophages from zymosan-treated animals but no additional inhibition resulted from PAF-AH treatment. In conclusion, zymosan peritonitis leads to priming of alveolar macrophages such that their subsequent tumor necrosis factor alpha response to LPS is enhanced. In vivo administration of PAF-AH abrogates this response, suggesting that this priming may be PAF dependent. This effect of PAF-AH may be mediated by the inhibition of intracellular signaling via inhibition of ERK kinase and NF-kappaB activation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1981

Complement proteins and macrophages. III. The production of factor B by particle-ingesting macrophages.

A kinetic study of factor B secretion by particle-ingesting macrophages showed that the ingestion of zymosan but not latex lead to an early suppression of factor B secretion followed by a significant enhancement. This dual response was proportional to the number of ingested zymosans. After a suppressive period of 24-48 hr, the ingested zymosan stimulated the synthesis of factor B. The response of acid phosphatase synthesis to ingested zymosan was the same as that of factor B, while the synthesis of lactic dehydrogenase proceeded without an early suppression. These results suggest that factor B should be considered an enzyme released into the lysosomes of macrophages.

Acid Phosphatase↗
PubMed1997

Anti-chemotactic activity of capsular polysaccharide of Cryptococcus neoformans in vitro.

In this study, we demonstrated the anti-chemotactic activity of the capsular polysaccharides (CPSs) isolated from each of the heavily (H)- and weakly (W)-encapsulated strains of Cryptococcus neoformans in vitro. The capacity for activation of the alternative complement pathway (ACP) of cells of the two C. neoformans strains in fresh human sera was comparable to that of zymosan (insoluble control), whereas the capacity for generation of the chemotactic factor (CF) of the cells of the two strains in fresh murine sera was markedly lower in the order H- < W-strain than that of zymosan. Conversely, the capacities for ACP activation and CF generation of the CPSs were extremely lower than those of lipopolysaccharide (LPS, soluble control). When zymosan-activated murine serum was incubated with CPS, both CPSs inhibited CF activity dose dependently. When zymosan-activated serum was incubated with heat-killed cells of each strain of C. neoformans, H and W, the CF activity of the treated sera decreased significantly, suggesting that CPS per se did not affect the neutrophils directly, but CPS absorbed CF. On the other hand, both CPSs were shown to possess the O-acetyl groups in their molecules by 1H-nuclear magnetic resonance spectroscopy. The de-O-acetylation of both CPSs increased the capacity for ACP activation to a level similar to that of LPS, and the de-O-acetylated CPS of both strains exhibited a lower ability to inhibit CF than did native CPS. Collectively, these results suggest that the anti-chemotactic activity of CPS accounts for its ability to absorb the CF which was mostly generated at the sites around the cell wall of whole cells via the ACP, thus suppressing the inflammatory response by preventing dispersal of CF to the extracellular space; and also that the O-acetyl group is partly, if any, involved in the mechanism for incompetence in ACP activation as well as the inhibition of CF.

Acetylation↗
PubMed1976

Hepatic erythropoietin: enhanced production in anephric rats with hyperplasia of Kupffer cells.

Erythropoietin (Ep) levels were assayed in serum of adult male rats subjected sequentially to (1) administration of colloidal carbon, Zymosan or their vehicles (2) sham operation or bilateral nephrectomy with and without subtotal hepatictomy, and (3) hypoxia (0.45-0.40 atmospheres of air for 6 h starting 1 h after the operation). In anephric rats these agents induced a significant potentiation of hypoxic Ep activity. Since they did not apparently modify the kinetics of exogenous Ep, it is postulated that this phenomenon is mediated by enhanced extrarenal Ep production. Both colloidal carbon and Zymosan induced hyperplasia of the reticuloendothelial system (RES). Moreover, subtotal hepatectomy almost abolished the Ep response to hypoxia evoked by Zymosan. The correlation between hyperplasia of hepatic RES and enhanced Ep production in anephric rats primed with these agents suggests that Kupffer cells constitute a major source for extrarenal Ep. Additionally, it is of interest that colloidal carbon and Zymosan did not significantly modify the renal production of Ep.

Animals↗