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 1,045 records · Page 58Linked to original sources
PubMed2000

Differences in the response to oxidative stress and mutant frequency in CD (Sprague-Dawley) and Fisher 344 rats due to an induced inflammatory response.

In this study, the rodent air pouch model was used to examine the production and processing of oxidative DNA damage in two strains of rats commonly used in toxicity testing. An inflammatory response was induced by injecting zymosan A (50 mg) into an air pouch on male CD (Sprague-Dawley [S-D]) and Fisher 344 (F-344) rats, and the animals were then sacrificed at 1, 3, 7, 14, and 28 days (n = 6 per time point per strain). Tissues from the lining of the air pouch were collected for 8-hydroxy-2'-deoxyguanosine (8-OH-dG) analysis and for paraffin embedding. Significant (P < 0.01) increases in 8-OH-dG were observed after 1 day in the DNA from cells lining the air pouch of zymosan A-treated versus control S-D (101.5 +/- 27.1 vs. 23.1 +/- 2. 7 8-OH-dG/dG x 10(5)) and F-344 (51.4 +/- 5.3 vs. 14.4 +/- 0.6 8-OH-dG/dG x 10(5)) rats. By 28 days, 8-OH-dG levels had returned to background in S-D rats, but remained elevated in F-344 rats. The frequency of apoptosis was evaluated using the in situ end-labeling (TUNEL) assay, which revealed that zymosan A-treated S-D rats had a significantly (P < 0.05) higher frequency of apoptosis compared to zymosan A-treated F-344 rats. To examine the potential consequences of these differences in endogenously produced DNA damage and apoptosis, we measured mutations at the hprt locus in fibroblasts of the pouch lining and observed a significant (P < 0.05) increase in the mutant frequency at day 28 in F-344 rats (54.2 +/- 13.6 mutants per 10(6) cells) compared to controls (4.5 +/- 2.0 mutants per 10(6) cells). The mutant frequency was not increased in S-D rats. These data demonstrate that strain differences in the production and processing of oxidative DNA damage due to an inflammatory response may impact the long-term pathologic consequences of chronic inflammation. Environ. Mol. Mutagen. 35:336-342, 2000 Published 2000 Wiley-Liss, Inc.

Animals↗
PubMed1990

Predictive value of whole blood chemiluminescence in patients with alcoholic hepatitis.

Recent reports suggest that ethanol metabolism leads to reactive oxygen intermediates that may be responsible for the lesions observed in alcoholic hepatitis. This study investigated the production of reactive oxygen intermediates in peripheral blood phagocytes of patients with alcoholic hepatitis and attempts to evaluate its predictive value. Using a luminol-dependent chemiluminescence method, reactive oxygen intermediate production was measured directly within microamounts of whole blood, both in the absence (basal chemiluminescence production) and in the presence of phagocyte-stimulating agents including latex, zymosan, phorbol myristate acetate and N-formyl-methionyl-leucyl-phenylalanine. Thirty patients with well-documented and histologically proven alcoholic hepatitis were studied. Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function were used to assess the prognosis of the liver disease. Patients were followed up monthly for 6 mo. Results were compared with those obtained in 17 patients with nonalcoholic liver disease and in 78 normal control subjects. Basal chemiluminescence production was significantly higher in patients with alcoholic hepatitis than in those with nonalcoholic liver disease and in normal subjects (p less than 0.001). Chemiluminescence responses to latex, zymosan and phorbol myristate acetate were significantly lower in alcoholic hepatitis patients than in normal subjects (p less than 0.001); however, when compared with nonalcoholic liver disease patients, these responses were significantly decreased only in the presence of zymosan (p less than 0.05). Both basal chemiluminescence production (p less than 0.001) and zymosan-induced chemiluminescence responses (p less than 0.02) were closely related to alcoholic hepatitis prognosis indices (i.e., Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Relationships between oxidative metabolism, macrophage activation, and antilisterial activity.

Previous reports from this laboratory have revealed that macrophages obtained from 7-day Listeria-immune mice elicited 15 h before harvest with heat-killed homologous microorganisms were able to kill Listeria monocytogenes while resident or elicited cells were not [14, 16]. In the present study, experiments were conducted to determine if phagocytosis-associated oxidative metabolic activity participates in the enhanced destruction of Listeria by activated macrophages. Investigations into production of oxygen radicals by zymosan-stimulated macrophages revealed that Listeria-immune antigen-elicited (LIAE) cells produced significantly more superoxide and hydrogen peroxide than did resident, thioglycolate, or Listeria antigen-elicited macrophages. Additionally, the percentage of nitroblue tetrazolium (NBT) dye positive cells following exposure to zymosan was maximal in the immune-elicited population. Utilizing a luminol-dependent assay, a short-term chemiluminescent (CL) burst was noted in phagocytizing macrophages. This response was greatest in the LIAE population that exhibited a tenfold increase in peak chemiluminescence over other cell types. Prolonged in vitro culture of these cells diminishes their capacity to generate oxygen radicals. Additionally, LIAE macrophages cultured in excess of 38 h exhibited a significant decrease in zymosan-stimulated hydrogen peroxide release while the decline in superoxide generation was minimal. A substantial diminution in the Listeria-stimulated CL response was also noted during this time period. However, phagocytosis of Listeria by LIAE cells failed to induce the level of oxygen metabolites seen when zymosan was used as the particulate stimulant. In addition, scavengers of oxygen radicals were found to be relatively ineffective in reducing the killing of L monocytogenes by immunologically activated macrophages in culture. It therefore appears that toxic oxygen species do not play a major role in the heightened killing of Listeria by activated macrophages.

Animals↗
PubMed1997

Liver cysteine proteinases in macrophage depression induced by gadolinium chloride.

Liver lysosomal enzymes during macrophage depression (gadolinium chloride, 7 mg/kg, intravenously) and macrophage stimulation (zymosan, 100 mg/kg, intravenously) have been studied. It was shown that gadolinium chloride treatment of rats reduced the rate of carbon particles phagocytosis at 24 and 48 h after the single administration. Decreased endocytic capacity of Kupffer cells was confirmed also by electron microscopy. Gadolinium chloride induced labilization of liver lysosomes (increased free activity of cathepsins B and L); there was no changes of specific activity of liver cysteine proteinases (24 h). Gadolinium chloride prevented death of rats after administration of non-sonicated particular zymosan particles, resulting to 70% survival, compare with the 17% survival in group with zymosan alone. We can summarize that macrophages depression by gadolinium chloride abolish symptoms of inflammation in zymosan-model, influencing on cysteine proteinases of Kupffer cells.

Animals↗
PubMed1992

Activated human peripheral blood neutrophils produce epithelial injury and fibronectin breakdown in vitro.

The ability of peripheral blood neutrophils to injure elements of the alveolar septum was assessed. Experiments consisted of activating previously isolated neutrophils (PMNs) with a soluble (phorbol myristate acetate, PMA) and a particulate (zymosan) trigger, and measuring detachment of 51Cr-labeled epithelial cells. In addition, the mechanisms of epithelial injury were investigated by including anti-proteinase and antioxidants in the system. Untriggered PMNs produced only slight detachment injury to epithelial cells at two effector-target cell ratios, this effect being dramatically increased after triggering with PMA; zymosan caused triggering but less than was produced by PMA. Alpha-1-protease inhibitor produced a decrease in detachment when both PMA- and zymosan-triggered cells were the effectors; superoxide dismutase did not significantly reduce detachment. The ability of triggered PMNs to cause proteolysis of fibronectin, as measured in a radiolabeled fibronectin matrix degradation assay, was related to their triggerability in the detachment assay, zymosan being largely ineffective in triggering enhanced proteolysis. These findings suggest that fibronectin is important in maintaining the integrity of the alveolar epithelial surfaces. Furthermore, in inflamed alveoli, activated PMNs can release proteinases, which cause degradation of this matrix component leading to compromise of the alveolar epithelial barrier.

Cell Adhesion↗
PubMed2004

CD44 and hyaluronic acid regulate in vivo iNOS expression and metalloproteinase activity in murine air-pouch inflammation.

OBJECTIVE: To evaluate the effects of anti-CD44 IM7.8.1 antibody, HMW-HA and LMW-HA on leukocyte migration and adhesion, and the induction of proinflammatory mediators, in mouse air-pouch inflammation induced by zymosan. METHODS: Leukocytes were obtained from zymosan-air pouches after the intra-pouch injection of anti-CD44 IM7.8.1, isotype control, HMW-HA, LMW-HA or PBS. TNF-alpha, IL-1beta and iNOS mRNA were estimated in leukocytes by semi-quantitative RT-PCR. Matrix metalloproteinases (MMPs) from exudates were evaluated by zymography and Western Blot. Adhesion and migration of leukocytes were evaluated in HA-coated plates and Boyden chambers respectively. RESULTS: IM7.8.1 decreased iNOS mRNA levels and the activity of both MMP-9 and MMP-2 eight h after injection into zymosan air pouch while IM7.8.1, HMW-HA and LMW-HA had no effect on IL1-beta or TNF-alpha mRNA levels. Leukocytes from air pouch adhered to and migrated in vitro against both HMW-HA and LMW-HA. LMW-HA increased the number of leukocytes in the air pouch and iNOS mRNA levels as compared to PBS injection. In contrast, HMW-HA decreased leukocyte count and reduced iNOS mRNA levels. Paradoxically, the activity of both MMP-9 and MMP-2 was increased by HMW-HA and decreased by LMW-HA. CONCLUSIONS: Both CD44 and HA can modulate leukocyte migration and induction of proinflammatory mediators in mouse zymosan air pouch inflammation. IM7.8.1 had consistent anti-inflammatory effects, reducing iNOS, MMP-9 and MMP-2. HMW-HA and LMW-HA were able to modulate both the induction of proinflammatory mediators and leukocyte count in the air pouch.

Animals↗
PubMed1995

Dexamethasone and methylprednisolone affect rat peritoneal phagocyte chemiluminescence after administration in vivo.

Production of reactive oxygen compounds by peritoneal monocytes/macrophages was studied in rats exposed to dexamethasone or methylprednisolone in the drinking water. Luminol-amplified chemiluminescence was measured in preparations of peritoneal leukocytes activated ex vivo by serum opsonized zymosan, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). After dexamethasone administration for 1 day (approximately 0.13 mg/kg per 24 h) a significant reduction in chemiluminescence was found in cells stimulated with serum opsonized zymosan, while responses to fMLP and PMA stimulation were significantly reduced after 2 days. The maximal inhibition obtained after 5-8 days of dexamethasone administration (plasma levels < 5 nM) was 92.0 +/- 1.2%, 87.6 +/- 0.2% and 84.5 +/- 3.1% in cells stimulated with serum opsonized zymosan, fMLP and PMA, respectively. Administration of dexamethasone or methylprednisolone for 48 h gave a dose-dependent reduction of chemiluminescence. ED50 values of dexamethasone were estimated at 0.06-0.15 mg/kg for the different stimulators (plasma concentrations 5-10 nM). Estimated ED50 values for methylprednisolone were 35-36 mg/kg. Since the percentage of mononuclear phagocytes in the peritoneal cell population did not change significantly with dose or time of dexamethasone exposure, this study indicates that glucocorticoids have a depressive effect on the monocyte/macrophage 'respiratory burst' in vivo. The results are consistent with the hypothesis that these effects are mediated by glucocorticoid receptors. Although the pathway activated by serum opsonized zymosan was more rapidly inhibited than the fMLP- and PMA-activated pathways, the responses induced by the different stimulators were similarly affected, suggesting a modulation of common components in the activation pathways, possibly protein kinase C or the NADPH-oxidase complex, after administration of low pharmacological doses of glucocorticoids in vivo.

Animals↗
PubMed1988

Separation and chemiluminescence properties of human, canine and rat polymorphonuclear cells.

Human as well as canine and rat polymorphonuclear cells (PMN) were separated from whole blood by centrifugation. Two-step discontinuous Percoll gradients with distinct densities were used. The purity of the preparations was 99.2%, 98.4% and 97.9%, respectively and the corresponding recoveries were 80.1; 66.3% and 69%. The chemiluminescence properties of the isolated PMN and of phagocytes in small quantities of whole blood were compared in luminol-enhanced assays after stimulation with various agents: non-opsonized zymosan (3.5 g/l), phorbol myristate acetate (PMA, 2.8 X 10(-6) M), calcium ionophore A 23187 (10(-5) M) and N-formyl-methionyl-leucyl-phenylalanine (FMLP, 3.5 X 10(-6) M). The isolated cells of the three species responded to all of the various stimuli. Species-related sensitivity followed the order: human greater than canine greater than rat. Responses to the various agents in the human cells was ranked: PMA greater than or equal to A 23187 greater than zymosan greater than FMLP; for the dog: A 23187 greater than PMA greater than zymosan greater than FMLP; and for the rat: zymosan greater than or equal to PMA greater than FMLP greater than or equal to A 23187. Time courses and peak maximum responses were different following stimulation in the absence or presence of autologous plasma. Distinct soluble stimuli resulted in maximum responses below the baseline in the whole blood assays with canine (FMLP) and rat (FMLP, A 23187) phagocytes.

Animals↗
PubMed1992

Decreased mesenteric blood flow in experimental multiple organ failure.

Disorders of mucosal blood flow may contribute to gut barrier dysfunction in multiple organ failure (MOF). We evaluated alterations of mesenteric microcirculation in a rat model of MOF. Male Wistar rats received 1 mg/g body weight of zymosan A in 4 ml of mineral oil by intraperitoneal injection and were studied on Days 1, 3, and 5 following injection. A control group received no zymosan. The experimental group also received a fluid resuscitation regimen of 0.9 N saline subcutaneously equal to 0.1 ml/g body weight on the day of zymosan injection and 0.05 ml/g body weight daily thereafter. Day 1 animals tended toward a statistically significantly lower mean arterial pressure versus controls (86.6 +/- 8 mm Hg versus 106 +/- 5 mm Hg, F = 0.09 by ANOVA). Significant arteriolar vasoconstriction occurred on Days 1 and 3 versus control (70 +/- 4 microns and 57 +/- 8 microns versus 96 +/- 3 microns, F = 0.0002). Laser doppler velocity, indicating red blood cell velocity, expressed as a percentage of control paralleled this vasoconstriction (70 +/- 9 and 72 +/- 7%, respectively). We conclude that mesenteric arteriolar vasoconstriction occurs accompanied by decreased red blood velocity. We believe that this is indicative of decreased mesenteric perfusion in this zymosan model of MOF and that survival to Day 5 is associated with a reversal of these microcirculatory changes.

Animals↗
PubMed1984

Identification of C3b as the major serum protein that stimulates prostaglandin and thromboxane synthesis by macrophages.

We have previously reported that heterologous, homologous and autologous sera, all stimulated rabbit alveolar macrophages to synthesize prostaglandins (PG). Gel permeation chromatography of serum showed multiple fractions possessing this stimulatory activity, with the major one at 150-160K daltons. In the present study, we have shown that: (a) Fresh rabbit serum stimulated PG release by macrophages. (b) Serum depleted of C3 and C5 lost its stimulatory activity. (c) Trypsinized serum, sera activated by aggregated IgG and zymosan, partially purified C3, C5 and the C3, C5 preparation or purified C3 activated by zymosan, all stimulated PG release by macrophages with the following order of potency: activated C3, C5 = activated C3 = zymosan-activated serum greater than trypsinized serum = aggregated IgG-activated serum greater than partially purified C3, C5 = serum. PGE2 was the predominant PG synthesized by stimulated macrophages. However, thromboxane (TX) production seemed to be more selectively enhanced i.e., increase in TX production was more pronounced than the increase in PGE release. To further identify the active complement component, we blocked the C3b receptor (C3 b R) by preincubating macrophages with anti-C3bR, and showed that subsequent treatment with activated C3 and C5 failed to elicit any PG release. This pretreatment with anti-C3bR had no inhibitory effect on subsequent zymosan stimulation of PG release. Thus we concluded that C3b was the major serum protein that stimulates PG synthesis by macrophages.

Animals↗
PubMed1982

Functional assessment of alveolar macrophages: comparison of cells from asthmatics and normal subjects.

Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from seven healthy nonallergic, nonasthmatic donors, 15 patients with allergic bronchial asthma, and six patients with aspirin-sensitive asthma. AM were purified by adherence over 2 hr and cultured for an additional 24 hr. Functional assessment of viable cells was carried out for zymosan phagocytosis and for prostaglandin (PG) E2-PGF2 alpha and thromboxane (Tx) B2 release by resting and zymosan-stimulated AM. The eosinophil count in BAL fluid from allergic asthmatics was higher than that from control subjects (3.9% +/- 1.6% vs 0.4% +/- 0.3%, p less than 0.05) and still greater in BAL from patients with aspirin-sensitive asthma (21.7% +/- 9.0%, p less than 0.01). After the 24 hr of incubation, the AM viability was inversely correlated to the percentage of eosinophils in BAL fluid (r = -0.54, n = 21, p less than 0.02). Zymosan phagocytosis was significantly lower by viable cells from both allergic asthmatics and aspirin-sensitive patients as compared with cells from normal donors (p less than 0.05). Zymosan phagocytosis induced a twofold to threefold increase in the release of PGE2, PGF2 alpha, and TxB2 from AM of normal subjects (p less than 0.01) but only a onefold to twofold increase from AM of allergic asthmatic patients. The stimulated AM from aspirin-sensitive patients released smaller quantities of each product than AM from normal subjects or allergic asthmatic patients (p less than 0.05). We conclude that the viability and functional activity of AM are impaired in asthmatic patients and that these deficits correlate with the percent eosinophilia in the BAL; it is therefore suggested that they may be due to an interaction between eosinophils and AM in the bronchoalveolar lumen.

Asthma↗
PubMed1986

Enhanced eosinophil luminol-dependent chemiluminescence in allergic rhinitis.

Eosinophils were isolated from patients with seasonal allergic rhinitis, and their functional activity was evaluated by their luminol-dependent chemiluminescence (CL) response to opsonized zymosan and phorbol 12-myristate 13-acetate (PMA). We found that eosinophils from patients with allergic rhinitis produced a significantly greater CL response to opsonized zymosan than did normal cells. Eosinophils from both subjects with allergic rhinitis and control subjects were isolated to a purity of 95% and elicited peak values of 1,101, 901 +/- 133,708 cpm/5 X 10(5) cells (n = 7) and 417,278 +/- 25,910 cpm/5 X 10(5) cells (n = 5), respectively. The enhanced eosinophil CL to zymosan was found at times when the patients were maximally symptomatic with hay fever symptoms to ragweed pollen and again when they were asymptomatic. Eosinophils from these patients with allergic rhinitis also had enhanced CL to PMA (0.01 mcg/ml), but this increased activity was largely limited to times of hay fever symptoms. No correlation was found between enhanced eosinophil CL activity and the number of circulating eosinophils in allergic individuals. In contrast to the increased eosinophil activity, neutrophil CL to zymosan and PMA was similar in allergic and normal individuals throughout the study. These data provide evidence for the existence of enhanced oxidative metabolic function in eosinophils from patients with allergic rhinitis and raise the possibility that this particular activity is important in hay fever.

Adult↗
PubMed1989

Methylprednisolone inhibits granulocytopenia induced by infusion of complement-activated serum but not of complement-activated plasma in rabbits.

The effect of methylprednisolone was examined on complement-induced granulocytopenia in vivo following infusion of zymosan-activated autologous plasma or serum into rabbits. Methylprednisolone only inhibited granulocytopenia and thrombocytopenia when zymosan-activated serum or fibrinogen-depleted plasma were infused. It was ineffective at preventing granulocytopenia in animals infused with zymosan-activated plasma. Only zymosan-activated plasma contained fibrin monomers which could directly cause granulocytopenia independently of the generation of C5a. Hence, during complement activation in whole blood in vivo, little or no effect of methylprednisolone should be expected in preventing granulocytopenia.

Agranulocytosis↗
PubMed1987

Differences in arachidonic acid release, metabolism and leukotriene B4 synthesis in human polymorphonuclear leukocytes activated by different stimuli.

Products of the 5-lipoxygenase pathway were analyzed after different stimuli in human polymorphonuclear leukocytes prelabeled with 3H-arachidonic acid. Upon stimulation with the Ca2+ ionophore, A23187, polymorphonuclear leukocytes generate 118.2 +/- 18 pg [3H]dihydroxyeicosatetraenoic acids (diHETEs, including 3H-leukotriene B4 and its 6-trans-stereoisomers), after exposure to serum coated zymosan (35.8 +/- 9 pg) and N-fMet-Leu-Phe (39.5 +/- 9 pg). Conversion of 3H-arachidonic acid paralleled its release after A23187 and fMet-Leu-Phe exposure leaving only 13.8 +/- 7% and 13.6 +/- 3% of the released 3H-arachidonic acid unmetabolized, respectively. In contrast, after stimulation with serum-coated zymosan only a small fraction of the released 3H-arachidonate was converted to 5-lipoxygenase products leaving 73.0 +/- 5% of the released 3H-arachidonic acid unmetabolized. In parallel, leukotriene B4 synthesis was studied in unlabeled polymorphonuclear leukocytes, resulting in 40 +/- 15 ng upon A23187 stimulation, 4 +/- 0.9 ng upon stimulation with fMet-Leu-Phe and 1.8 +/- 0.9 ng after serum-coated zymosan, showing a different ratio of leukotriene B4 to 3H-diHETE for A23187 in contrast to serum-coated zymosan and fMet-Leu-Phe. These results indicate that the coupling between the release of the precursor fatty acid and the metabolism via the 5-lipoxygenase pathway differs greatly between different stimuli.

Arachidonic Acids↗
PubMed1995

Effect of serotonin on the chemiluminescence response of rat peripheral blood leucocytes.

Serotonin (5-HT) has been shown to exert various immunomodulatory effects. In this study, the effects of 5-HT, 5-hydroxy-DL-tryptophan (5-HTP) and DL-p-chlorophenylalanine (PCPA) on the chemiluminescence (CL) responses of rat peripheral blood leucocytes (PBL) activated by phorbol myristate acetate (PMA), opsonized zymosan or latex beads were assessed. The CL responses were measured following in vitro treatment with 0.01-100 microM 5-HT, and either 1 h after the last i.p. administration of 5-HT (0.05, 0.5, 1, 2.5, 5 or 10 mg/kg for 4 days), 5-HTP (25 or 100 mg/kg for 4 days) or PCPA (200 mg/kg for 4 days, n = 5), or 48 h after a single 200 mg/kg PCPA injection. A concentration-dependent decrease in CL responses was noted following in vitro 5-HT treatment. In vivo treatment of rats with 5-HT produced a reverse bell-curve inhibiting effects on the CL response with a maximal inhibition in rats receiving 1 mg/kg/day 5-HT and a weaker response of PMA-activated PBL. In vivo treatment with high-dose 5-HTP increased CL response of opsonized zymosan-activated PBL, while low-dose 5-HTP decreased CL response of opsonized zymosan and latex beads-activated PBL. No effect was observed in PMA-activated PBL from rats treated with 5-HTP. By contrast, in vivo treatment with PCPA increased CL responses induced by PMA or latex beads, whereas CL responses using opsonized zymosan were not significantly affected. These results suggest that 5-HT modulates the CL response of rat leucocytes to particulate stimuli.

5-Hydroxytryptophan↗
PubMed2006

Mechanism of macrophage activation by (1,4)-alpha-D-glucan isolated from Tinospora cordifolia.

The signaling mechanism of the novel (1,4)-alpha-D-glucan (RR1) isolated from the medicinal plant Tinospora cordifolia was investigated in macrophages to evaluate its immunostimulating properties. When RAW264.7 macrophages were incubated with RR1 at 4 degrees C, the novel glucan inhibited the phagocytosis of unopsonized zymosan A bioparticles in a dose-dependent manner. RR1 also inhibited the binding and internalization of opsonized zymosan A bioparticles, although at a lower level than laminarin. Incubation of macrophages with anti-CD11b mAb followed by RR1 failed to show any inhibitory effect on RR1-induced TNF-alpha synthesis confirming that complement receptor 3 (CR3) is not involved in the opsonic binding and internalization of RR1 in macrophages unlike zymosan A. The anti-CD11b mAb has significant inhibitory effect on the zymosan A-induced tumor necrosis factor (TNF)-alpha synthesis. RR1 induced TNF-alpha synthesis in macrophages in a dose-dependent manner which can be completely inhibited by the NF-kappaB inhibitor caffeic acid phenethyl ester (CAPE) or curcumin. RR1 activated NF-kappaB in a time- and dose-dependent manner and this modulation of nuclear NF-kappaB activity is associated with the degradation of I-kappaB alpha thus facilitating the translocation of NF-kappaB into the nucleus. RR1-induced NF-kappaB activity peaks at 8 h of RR1 stimulation while I-kappaB alpha degradation occurred within 1 h of stimulation. RR1-induced NF-kappaB activation occurred through TLR6 signaling as evidenced by the synthesis of IL-8 in TLR6-transfected HEK293 cells. These results show that the novel (1,4)-alpha-D-glucan from Tinospora cordifolia activates the immune system through the activation of macrophages that occurs through TLR6 signaling, NF-kappaB translocation and cytokine production.

Animals↗
PubMed2005

Neuropeptide Y and its receptor subtypes specifically modulate rat peritoneal macrophage functions in vitro: counter regulation through Y1 and Y2/5 receptors.

It is well documented that neuropeptide Y (NPY) exerts a wide range of biological functions through at least five NPY Y receptor subtypes (Y1-Y5), but its immunological effects only recently came into focus. Using NPY family peptides and NPY-related receptor-specific peptides as well as Y1 and Y2 receptor antagonists, we have tested which NPY Y receptors are involved in NPY-induced modulation of rat peritoneal macrophage function in vitro. NPY and PYY increased oxidative burst in phorbol myristate acetate (PMA)-stimulated macrophages involving activation of protein kinase C (PKC), and decreased it in zymosan-stimulated cells resembling inhibition of signaling pathways subsequent to binding of zymosan particles for the iC3b fragment receptor on macrophages. The combined treatment with NPY and NPY Y receptor antagonists revealed that NPY-induced potentiation of oxidative burst in PMA-stimulated cells is mediated through Y1 and Y2 receptors, while NPY-induced suppression in zymosan-stimulated cells is mediated through Y2 receptors only. NPY-related peptides differently modulated macrophage function, confirming involvement of NPY Y2 receptor in both potentiation and suppression of oxidative burst in these cells. Additionally, it was shown that NPY Y5 receptor mediated suppression of oxidative burst in PMA- and zymosan-stimulated macrophages. Taken together, the present data reveal an NPY Y1 and Y2/Y5 receptor interaction in NPY-induced modulation of macrophage functions related to inflammation.

Animals↗
PubMed1992

Correction of deficient phagocytosis during erythropoietin treatment in maintenance hemodialysis patients.

Studies on the influence of erythropoietin (EPO) on granulocyte or monocyte function are scant. In this study, the effect of EPO on polymorphonuclear cell (PMN) respiratory burst activity was evaluated in a double-blind, placebo-controlled study in 22 patients on maintenance hemodialysis. As an index of phagocyte respiratory burst activity, the increase in 14CO2 production from labeled glucose-1-C, after challenge with latex and zymosan, was measured on predialysis whole blood samples, before and after EPO-treatment. As controls, 56 nonuremics and 49 non-EPO-treated hemodialysis patients were evaluated. Before EPO treatment 14CO2 production was depressed to 75.7% (latex) and 54.6% (zymosan) of healthy controls (P less than 0.01). A marked improvement was observed after a mean treatment period of 4 months (latex, 115 +/- 12 to 172 +/- 14; zymosan, 178 +/- 19 to 412 +/- 36 dpm/10(3) PMN, P less than 0.01). Placebo treatment induced no changes. The improvement became more pronounced with prolongation of treatment. A significant correlation between hematocrit and 14CO2 production was observed in the EPO treatment group (latex: n = 44, r = 0.47, P less than 0.05; zymosan: n = 44, r = 0.57, P less than 0.001). No correlation was found with serum ferritin. We conclude that the depressed phagocyte glycolytic activity of hemodialyzed uremics is normalized during correction of anemia by EPO. This may be attributed to factors other than a reduction in the body iron stores.

Adult↗