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PubMed1988

Effects of monocyte macrophages stimulation on hepatic lipoprotein receptors.

The first series of in vivo experiments were designed to investigate the effects of monocytic macrophages (MM phi) stimulation by zymosan in cholesterol-fed rats. We found that the MM phi stimulation significantly decreased plasma very-low-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol but not high-density lipoprotein-cholesterol. The hepatic and aortic cholesterol levels were also significantly decreased; meanwhile, the biliary total bile acid and fecal sterol excretion were significantly enhanced. These results were beneficial to the prevention and regression of atherosclerosis. The second series of in vitro experiments led to the discovery that zymosan did not have effect on HDL and LDL binding, uptake and degradation of hepatic parenchymal and nonparenchymal cells isolated from normal rats, but did have significant effects on those isolated from cholesterol-fed rats. The experiments of Kupffer cells modulating hepatocytes also demonstrated that hepatocyte HDL receptor activity was significantly enhanced by conditioned medium from acetylated LDL plus zymosan added to Kupffer cells. Bmax of 125I-labeled HDL specific binding was increased from 237.8 to 295.2 ng/mg cell protein. The Ka value was not affected, indicating that there might be an increment in receptor number, but not receptor affinity. Cholesterol-loaded zymosan-stimulated Kupffer cells might secrete a soluble mediator affecting hepatocyte HDL receptor activity. Zymosan and other MM phi-stimulating reagents are promising in the exploration of a new approach for prevention and treatment of hypercholesterolemia and atherosclerosis.

Animals↗
PubMed1987

Inhibition of complement-mediated hepatic thromboxane production by mepacrine, a phospholipase inhibitor.

Complement-mediated thromboxane production in the isolated, perfused rabbit liver has been shown to be calcium sensitive. The present study utilizes mepacrine, a phospholipase inhibitor, to investigate the involvement of phospholipases A and C in the mechanism of complement-induced arachidonate metabolism. Livers perfused in vitro in an open, nonrecirculating system were given either normal plasma or zymosan activated plasma at a rate of 1 ml/minute for 10 minutes. An additional group of livers was constantly perfused with 10 microM mepacrine while receiving the zymosan activated plasma infusion. Control group livers demonstrated a stable perfusion pressure, rate of release of lactic dehydrogenase and acid phosphatase, and stable rates of thromboxane and prostacyclin production for the entire experimental period. In contrast, treatment with zymosan-activated plasma resulted in significant increases in the rate of thromboxane B2 release at 1, 3 and 5 minutes of infusion when compared to the values of the control group. Neither prostacyclin release nor enzyme release changed significantly as a result of the zymosan-activated plasma administration. Treatment of the perfused livers with mepacrine abolished the complement-mediated production of thromboxane B2. In summary, this study has confirmed that plasma which has had its complement components activated by zymosan induces a transient, self-limiting production of thromboxane-like materials in the perfused rabbit liver. The mechanism of this stimulation is hypothetized to be a mepacrine-sensitive activation of phospholipase.

Acid Phosphatase↗
PubMedDate not supplied

Immunostimulation of tiger shrimp (Penaeus monodon) hemocytes for generation of microbicidal substances: analysis of reactive oxygen species.

NBT staining was used to determine the presence of superoxide anions (O2-) produced by tiger shrimp (Penaeus monodon) hemocytes attached to a coverslip. When cells were treated with beta-glucan, blue granules were observed in 41% of studied hemocyte cytoplasm. For zymosan-treated, PMA-treated, and control cells, the percentages of hemocytes showing similar blue granules were 31, 9, and 5%, respectively. A comparison of stimulative effects on 15 hemocyte suspensions, each collected from a single tiger shrimp, showed that beta-glucan had the strongest effect on intracellular O2- generation, followed by zymosan and PMA (2.5, 2, and 1.3 times greater than the O2- generated by the control group, respectively). After oxidizing phenol red to measure the amounts of hydrogen peroxide (H2O2) produced by the hemocytes, we found that beta-glucan had the strongest stimulative effect (12.2 nmol/mg protein), followed by zymosan and PMA (7.2 and 2.6 nmol/mg, respectively). However, a luminol-enhanced chemiluminescence analysis of hypochlorites (OCl-) produced by the experimental hemocytes showed that neither zymosan nor beta-glucan had a stimulative effect on OCl- production. However, following PMA stimulation, hemocyte chemiluminescence was detected although only at 1.7 mV. Using H2O2 as substrate and guaiacol as an electron acceptor, the enzyme activity of crude enzyme extract derived from broken hemocytes was analyzed; enzyme activity similar to that of human myeloperoxidase (MPO) (0.104 U/mg protein) was observed. The data showed that only PMA had any stimulative effect on MPO-like enzyme activity (2.23 times that of the control group); zymosan and beta-glucan did not have any observable effects on this specific enzyme activity. This is the first documented demonstration of a respiratory burst in shrimp hemocytes.

Animals↗
PubMed1989

A role for protein kinase C-mediated phosphorylation in the mobilization of arachidonic acid in mouse macrophages.

Mouse peritoneal macrophages respond to activators of protein kinase C and to zymosan particles and calcium ionophore by rapid enhancement of a phospholipase A pathway and mobilization of arachidonic acid. The pattern of protein phosphorylation induced in these cells by 4 beta-phorbol 12-myristate 13-acetate (PMA), 1,2-dioctanoyl-sn-glycerol, exogenous phospholipase C and by zymosan and ionophore A23187 was found to be virtually identical. The time course of phosphorylation differed among the phosphoprotein bands and in only some of those identified (i.e., those of 45 and 65 kDa) was the phosphorylation sufficiently rapid to be involved in the activation of the phospholipase A pathway. Phosphorylation of lipocortin I or II could not be detected. Down-regulation of kinase C by a 24-h pretreatment with PMA resulted in extensive inhibition of both protein phosphorylation and the mobilization of arachidonic acid in response to PMA or dioctanoylglycerol. The phosphorylation of the 45 kDa protein in response to zymosan and A23187 was also inhibited by pretreatment with PMA, while only arachidonic acid release induced by zymosan was inhibited by this pretreatment. Depletion of intracellular calcium had little effect on kinase C-dependent phosphorylation, although arachidonic acid mobilization is severely inhibited under these conditions. Bacterial lipopolysaccharide and lipid A induced a phosphorylation pattern different from that induced by PMA, and down-regulation of protein kinase C did not affect lipopolysaccharide-induced protein phosphorylation. The results indicate (i) that protein kinase C plays a critical role also in zymosan-induced activation of the phospholipase A pathway mobilizing arachidonic acid; (ii) that such activation requires calcium at some step distal to kinase C-mediated phosphorylation and (iii) that phosphorylation of lipocortins does not explain the kinase C-dependent activation.

Animals↗
PubMed1981

Inactivation during phagocytosis of leucine aminopeptidase, an ecto-enzyme of polymorphonuclear neutrophils.

Changes in enzyme activities of the plasma membrane markers were examined during phagocytosis using guinea-pig polymorphonuclear neutrophils. Incubation of neutrophils with fresh serum-opsonized zymosan particles showed a significant reduction in leucine aminopeptidase activity, whereas 5'-nucleotidase and alkaline phosphodiesterase activities remained unchanged. Inactivation of leucine aminopeptidase activity was also observed by exposure of neutrophils to complement-opsonized zymosan particles, but not to non-opsonized zymosan, IgG-coated zymosan or polystyrene latex particles. Pretreatment of neutrophils with cytochalasin B, which prevents phagocytosis but not surface binding of particles, provoked inactivation to the same degree as when the cells were allowed to phagocytose the particles. However, the inactivation during phagocytosis was protected by serine protease inhibitors. These findings suggest that loss of leucine aminopeptidase activity from phagocytosing cells may be mediated by certain serine protease inhibitor-sensitive factor(s) which are probably activated by the attachment of an opsonized zymosan particle to a specific membrane receptor, probably the C3b receptor.

Animals↗
PubMed1995

Differential regulation of phospholipase D and phospholipase C by protein kinase C-beta and -delta in liver macrophages.

We have studied activation of phospholipase (PL) C and PLD in liver macrophages labelled with [3H]arachidonic acid. Zymosan, phorbol 12-myristate 13-acetate (PMA), A23187 and fluoride but not arachidonic acid or lipopolysaccharide (LPS) induce an activation of PLD ([3H]phosphatidylethanol (PEt) accumulation). An activation of PLC ([3H]diacylglycerol (DAG) accumulation) is measured with zymosan, PMA and fluoride but not with A23187, LPS or arachidonic acid whereas inositol phosphates are formed with zymosan, only. Removal of extracellular calcium reduces the formation of [3H]PEt and [3H]DAG while pretreatment of the cells with dexamethasone reduces [3H]PEt formation, only. PMA- and zymosan-induced activation of PLD and PMA-induced activation of PLC both seem to be mediated by protein kinase (PK) C-beta whereas zymosan-induced activation of PLC is negatively controlled by PKC-delta. We could furthermore present evidence that the release of [3H]arachidonic acid in these cells occurs independent of an activation of PLD.

Animals↗
PubMed2005

CpG DNA/zymosan complex to enhance cytokine secretion owing to the cocktail effect.

Zymosan, classified among beta-(1-->3)-d-glucans, is produced from the cell wall of yeast and well known to induce proinflammatory cytokines when ingested by immune cells. We found that zymosan forms a complex with immunostimulatory CpG DNA, where both zymosan and CpG DNA can induce cytokine secretion according to the different mechanisms (i.e., recognized by different receptors). The complex activated macrophages and induced cytokine secretion, more efficiently than separate administration of zymosan or CpG DNA. Microscopic observation showed that this increment of the cytokine secretion can be explained by the fact that zymosan and zymosan/CpG DNA complex are up-taken more than naked CpG DNA. Additionally, existence of two different immunostimulants in the same cells may enhance the immunoresponse. This report presents a new strategy to construct a delivering vehicle for CpG DNA and to enhance its activity with the 'cocktail effect' of the two immunostimulants.

Animals↗
PubMed2006

Mannan-binding lectin (MBL)-mediated opsonization is enhanced by the alternative pathway amplification loop.

The complement system is a humoral effector in the innate immune system. Three activation pathways exist in the complement system, known as the classical pathway, the lectin pathway and the alternative pathway. Dysfunction of lectin pathway activation is caused by MBL deficiency. MBL deficiency in a cohort of healthy Caucasian blood bank donors was investigated with MBL genotyping and MBL plasma concentration. Recognition of the yeast-derived zymosan by MBL was investigated with Western blot. The involvement of the alternative pathway amplification loop in enhancing MBL-mediated opsonization of zymosan was investigated in a novel opsonophagocytosis assay for flow cytometry. Sera deficient for MBL, factor D or properdin were tested, and purified MBL, factor D or properdin were used to recover opsonization. The optimal receiver-operator characteristic (ROC) cut-off value for dividing the Caucasian cohort in MBL-sufficient and MBL-deficient was calculated at 0.7 microg/ml. Thirty-eight percent of the group had concentrations below 0.7 microg/ml. Zymosan eluates opsonized with MBL-sufficient sera contain high oligomers of MBL, while eluates from MBL-deficient donors contained hardly any MBL. The MBL-, factor D- and properdin-deficient sera showed reduced opsonophagocytosis by human control neutrophils, as compared to normal MBL-sufficient sera. This reduction in opsonization was restored to normal levels by addition of purified MBL, factor D and properdin. The absence of opsonization in the factor D- and properdin-deficient sera, but presence in normal serum after blocking with anti-C1q-F(ab)2 and anti-MBL-F(ab)2, demonstrates the involvement of the amplification loop in MBL-initiated zymosan opsonization, even at very low serum concentrations (up to 3%, v/v). In conclusion, our data demonstrate that the MBL-mediated route of complement activation depends on the alternative pathway amplification loop for optimal opsonization of zymosan.

Cohort Studies↗
PubMed2001

Blockade of PAF receptors controls interleukin-8 production by regulating the activation of neutrophil CD11/CD18.

The production of interleukin-8 by neutrophils in response to particulate stimuli may play a role in the recruitment and activation of further neutrophils in an inflammatory reaction. Here, we have evaluated the sequence of early events leading to interleukin-8 production by phagocytosing neutrophils. Kinetic experiments showed that the phagocytosis of zymosan particles by human neutrophils was rapid in onset. In contrast, interleukin-8 production was more protracted and only detectable 6 h later. Nevertheless, inhibition of phagocytosis with cytochalasins B or D suppressed the late interleukin-8 production. Activation of neutrophils with zymosan failed to enhance CD11/CD18 expression on the neutrophil surface but led to an increase in the expression of an activation-dependent epitope on CD11/CD18. Pretreatment with the platelet-activating factor (PAF) receptor antagonist, UK-74505 (4-(2-chlorophenyl)-1,4-dihydro-3-ethoxycarbonyl-6-methyl-2-[4-(2-methylimidazol[4,5-c]pyrid-1-yl)phenyl]-5-[N-(2-pyridyl)carbamoyl]pyridine), significantly blocked the increase in the expression of the activation epitope, resulting in inhibition of the phagocytosis of zymosan and interleukin-8 production. In conclusion, the activation of neutrophils with zymosan leads to the activation of PAF receptors and this is followed by activation of CD11/CD18, phagocytosis of zymosan particles and subsequent interleukin-8 release.

CD11 Antigens↗
PubMed1999

A role for spinal nitric oxide in mediating visceral hyperalgesia in the rat.

BACKGROUND & AIMS: Intracolonic instillation of zymosan in rats produces hyperalgesia (i.e., facilitates the visceromotor response to colorectal distention) mediated by activity at spinal N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Nitric oxide (NO*) production often increases after NMDA receptor activation; NO* may then function as a further messenger. This study was designed to investigate the role of spinal NO* in this model of visceral hyperalgesia. METHODS: Zymosan or saline was given intracolonically, and the visceromotor response to noxious colorectal distention (80 mm Hg, 20 seconds) was measured 3 hours afterward. RESULTS: There was a significant enhancement of the visceromotor response in zymosan-, but not saline-treated, rats. This hyperalgesia was dose-dependently and reversibly attenuated by intrathecal administration of the nonselective NO* synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (100-800 nmol) as well as by the selective neuronal NOS inhibitor ARL 17477 (30-600 nmol). In support of these observations, there was a significant increase in the number of cells labeled for NADPH diaphorase or neuronal NOS in the lumbosacral spinal cord after intracolonic instillation of zymosan, but not saline. CONCLUSIONS: These data suggest that colonic inflammation induces the expression of neuronal NOS in the spinal cord and that increased production of spinal NO* is necessary for maintenance of zymosan-produced visceral hyperalgesia.

Abdominal Muscles↗
PubMed1998

Effects of particulate and soluble (1-3)-beta-glucans on Ca2+ influx in NR8383 alveolar macrophages.

Particulate and soluble (1-3)-beta-glucans are effective in preventing infections by enhancing macrophage and neutrophil functions. However, the mechanisms triggering these enhanced cellular responses are essentially unknown. We recently demonstrated that zymosan, a particulate (1-3)-beta-glucan receptor agonist, caused an influx of Ca2+ in NR8383 rat alveolar macrophages (AMs) and a resulting increase in intracellular Ca2+ (Zhang et al., J. Leukoc. Biol. 62 (1997) 341-348). Since Ca2+ is important in mediating leukocyte responses, we investigated whether other (1-3)-beta-glucans also alter Ca2+ mobilization in AMs. Particulate and soluble (1-3)-beta-glucans derived from Saccharomyces cerevisiae were used in these studies. Like zymosan, particulate (1-3)-beta-glucan (WGPs) caused a concentration-dependent increase in [Ca2+]i, which was inhibited by removal of extracellular Ca2+ and by SKF96365, an inhibitor of receptor-operated Ca2+ channels. When three different soluble (1-3)-beta-glucans, with molecular weights of approximately 11,000, 150,000, and 1,000,000 Da, were tested alone for effects on Ca2+ responses, the low molecular weight (1-3)-beta-glucan produced no effect and the intermediate and high molecular weight (1-3)-beta-glucans caused only a small increase in [Ca2+]i. Interestingly, however, all three soluble (1-3)-beta-glucans could significantly reduce the Ca2+ responses induced by a subsequent exposure to either WGPs or zymosan. These results demonstrate that: 1) particulate (1-3)-beta-glucan activates Ca2+ influx in NR8383 macrophages through receptor-operated Ca2+ channels; 2) soluble (1-3)-beta-glucans do not strongly activate Ca2+ influx in these cells; and 3) soluble (1-3)-beta-glucans significantly inhibit Ca2+ influx induced by WGPs or zymosan. Soluble (1-3)-beta-glucans are likely to prevent Ca2+ influx by competitively binding to the (1-3)-beta-glucan receptors recognizing zymosan and WGPs. The smaller Ca2+ influx induced by soluble (1-3)-beta-glucans may represent only a partial activation of post-receptor signal transduction pathways necessary for inducing Ca2+ influx.

Adjuvants, Immunologic↗
PubMed1999

Inhibition of Ca2+ influx by pentoxifylline in NR8383 alveolar macrophages.

Pentoxifylline (PTF), a phosphodiesterase (PDE) inhibitor, can prevent inflammation and tissue damage in animal and in vitro human studies. However, the underlying mechanism remains unclear. Since Ca2+ is a critical signal regulating the release of inflammatory mediators in macrophages, the effects of PTF on Ca2+ influx were examined in NR8383 alveolar macrophages (AMs). PTF induced a dose-dependent inhibition on Ca2+ influx activated by zymosan and by protein kinase C (PKC) activators 1,2-dioctanoyl-sn-glycerol (DOG) or phorbol-12-myristate 13-acetate (PMA). The inhibition appeared to be specifically on the receptor-operated Ca2+ entry. The capacitative Ca2+ entry was not affected by PTF. The inhibition was not due to altered cAMP levels since the zymosan-activated Ca2+ influx was not affected by the adenylate cyclase activator forskolin, nor by dibutyryl cAMP. Pretreatment with protein tyrosine kinase (PTK) inhibitor genistein abolished zymosan-induced, but not DOG-induced Ca2+ influx, suggesting that PTK is an upstream element of the signaling cascade and not the target of PTF. The Ca2+ entry activated by zymosan and by PKC activators was inhibited by the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Moreover, activation of MAPK by C6-ceramide (C6C) triggered a similar Ca2+ influx as elicited by zymosan and PKC activators, suggesting that MAPK is an element of the pathway. The C6C-induced Ca2+ influx was also inhibited by PTF. These results indicate that PTF blocks the receptor-operated Ca2+ influx in NR8383 AMs by inhibiting PDE which may acts as a downstream element of the signaling pathway or by direct interaction with Ca2+ channels.

Animals↗
PubMed2000

Differences in the changes of allergen-specific IgE serum levels and the chemiluminescence of peripheral blood phagocytes in patients with allergic rhinoconjunctivitis during the ragweed season.

The objective of this study was to compare the changes in the values of allergen-specific serum IgE levels and zymosan-induced whole blood chemiluminescence (CL) in 41 patients who had exclusively only ragweed allergy in the season of acute symptoms of disease in July, August and September. All patients had allergic rhinitis or rhinoconjunctivitis. Each patient was investigated as a self-control. The ragweed-specific IgE levels were measured by enzyme immunoassay (EIA). The luminol amplified zymosan-induced CL of whole human blood was detected. The allergen-specific serum IgE levels showed slight, but not significant, gradually increasing elevations during the whole season. On the other hand, significant increases were found in the values of the basal but especially in the zymosan-stimulated CL of peripheral blood phagocytes during the acute phase of allergy. Both the basal and the zymosan-induced CL reflected significantly the activated state of the immune system. These observations clearly show that there are well detectable signs of the systemic activation of the immune system in allergic rhinoconjunctivitis beside the local alterations. In addition, the measurements of the basal and zymosan-induced CL of peripheral phagocytes could clearly reflect the clinical state of disease in vitro.

Adult↗
PubMed1988

Release of lysosomal enzymes is not correlated with superoxide and prostaglandin production by stimulated rat Kupffer cells in primary culture.

A substantial production of prostaglandin E2 (PGE2) was induced in primary cultures of rat Kupffer cells by zymosan, calcium ionophore A23187, phorbol ester and arachidonic acid, whereas contact with latex particles, glucan or immunocomplexes led to a minor PGE2 release only. Superoxide generation, on the other hand, was observed after administration of zymosan, glucan and the phorbol ester but not after treatment with the calcium ionophore, arachidonate, latex particles or immunocomplexes. Lysosomal enzymes like beta-glucuronidase and N-acetyl-beta-D-glucosaminidase were detected in the medium of rat Kupffer cells in primary culture after contact with zymosan or calcium ionophore A23187. Other particulate matter, e.g., latex particles, glucan and immunocomplexes, lipopolysaccharides or soluble agents such as phorbol ester, arachidonic acid and gamma-interferon did not provoke the release of lysosomal enzymes. The activities of beta-glucuronidase and N-acetyl-beta-D-glucosaminidase found following prolonged exposure to zymosan or to A23187 were accompanied by the appearance of typical cytosolic enzymes like lactate dehydrogenase and glucose-6-phosphate dehydrogenase in similar proportions and with the same time course. The release of lysosomal enzymes seen after administration of zymosan or calcium ionophore is thought to be the result of unspecific leakage rather than a specific response of elicited Kupffer cells.

Acetylglucosaminidase↗
PubMed1998

Role of glutamate receptors and nitric oxide in the rostral ventromedial medulla in visceral hyperalgesia.

The present study was undertaken to examine the involvement of descending pain modulatory systems from the brainstem rostral ventromedial medulla (RVM) in modulating visceral hyperalgesia produced by intracolonic instillation of zymosan. Three hours after intracolonic zymosan, the visceromotor response (VMR) to noxious colorectal distension (CRD, 80 mmHg, 20s) was increased significantly. This hyperalgesia was attenuated in a dose-dependent manner by the selective NMDA receptor antagonist APV (10-30 fmol, 1 microl) microinjected into the RVM. The hyperalgesia was also attenuated by intra-RVM administration of the nitric oxide synthase (NOS) inhibitor L-NAME. In support, there was a significant increase in the number of cells in the RVM labeled for NADPH diaphorase (NADPH-d) or neuronal NOS (nNOS) in zymosan-treated rats. In contrast to the effects of APV and L-NAME, administration of the non-NMDA receptor antagonist DNQX into the RVM further enhanced the already facilitated VMR to CRD in zymosan-treated rats. Taken together, these data suggest that zymosan-produced visceral hyperalgesia is influenced by two descending pain modulatory systems: a facilitatory system mediated by activation of NMDA receptors in the RVM and production of nitric oxide, and an inhibitory system mediated by activity at non-NMDA receptors in the RVM. The unmasking of one system by selective blockade of the other suggests simultaneous activation of both by colonic inflammation.

2-Amino-5-phosphonovalerate↗
PubMed1991

Cytosolic calcium ion and arachidonic acid release and metabolism in macrophages.

The aim of the present work was to elucidate the role of cytosolic calcium ions, [Ca2+]i, in the control of arachidonic acid release and metabolism. [Ca2+]i was measured in resident peritoneal rat macrophages loaded with Fura2, and compared with the release of leukotriene B4(LTB4) and prostaglandin l2 (PGL2, assayed through its hydrolysis product 6-keto-PGF1 alpha). The calcium ionophore A 23187 stimulated both an increase in [Ca2+]i and the release of LTB4 and 6-keto-PGF1 alpha. On the contrary, zymosan and opsonized zymosan, while stimulating eicosanoid release to an extent only slightly lower than A 23187, did not affect [Ca2+]i. Lipopolysaccharide stimulated 6-keto-PGF1 alpha, but not LTB4, release, without affecting [Ca2+]i. In parallel experiments, macrophages were prelabelled with [3H]arachidonic acid and the release of total 3H-products was assayed and taken as an index of phospholipase activity. A 23187, zymosan and opsonized zymosan increased the release of 3H-products in the presence of Ca2+. When extracellular Ca2+ was removed, the ionophore-induced 3H-products release was greatly blunted, while the release induced by zymosan was actually augmented. Our data indicate that a generalized [Ca2+]i increase is not necessary for arachidonic acid release and metabolism in rat peritoneal macrophages.

Animals↗
PubMed2002

Immunomodulatory and anti-inflammatory effects of Kalanchoe brasiliensis.

The immunomodulatory effect of juice obtained from leaves of Kalanchoe brasiliensis (Kb) on zymosan-induced inflammation was investigated. C57B110 mice received a subcutaneous injection of 150 microg zymosan in the footpad. After 7 days, there was an increase in footpad thickness from 176 +/- 4 to 236 +/- 9 x 10(-2) mm and in blood flow in the footpad area, monitored by 99mTc, from 98 +/- 4 to 694 +/- 59 counts per minute (cpm). Zymosan induced a severe infiltration of leukocytes into the articular tissues and a 13-fold increase in the adjacent popliteal lymph node (PLN) weight. Beginning 2 days after the injection, mice were treated daily for 5 days with different concentrations of lyophilised Kb juice dissolved in water. Treatment with 480 mg/kg/day reduced footpad thickness to 193 +/- 5 x 10(-2) mm, leukocyte infiltration and blood flow to 150 +/- 18 cpm in the footpad area. PLN weight in zymosan-injected mice decreased from 6.5 +/- 0.5 to 1.5 +/- 0.4 mg, similarly to the decrease after treatment with indomethacin (3 mg/kg/day). Flow cytometric analysis of lymph node cells showed an important reduction in B cell number in Kb-treated mice. Treatment over a period of 10 days was also effective at reducing zymosan-induced inflammation, even when started 7 days after injection. These data suggest anti-inflammatory and immunosuppressive effects of K. brasiliensis that may account for its popularity in folk medicine against rheumatic diseases.

Adjuvants, Immunologic↗
PubMed2004

Stimulus-specific defect in the phagocytic pathways of annexin 1 null macrophages.

The role of the glucocorticoid-regulated protein annexin 1 during the process of phagocytosis has been studied using annexin 1 null peritoneal macrophages. Wild type and annexin 1 null macrophages were incubated with several distinct phagocytic targets. No differences were observed in rate or the maximal response with respect to IgG complexes or opsonised zymosan phagocytosis, as assessed by monitoring the production of reactive oxygen species. When annexin 1 null macrophages were incubated with non-opsonised zymosan particles, they exhibited impaired generation of reactive oxygen species, which was linked to a defect in binding of cells to the particles, as determined with fluorescent zymosan. This phenomenon was further confirmed by electron microscopy analysis, where annexin 1 null macrophages internalised fewer non-opsonised zymosan particles. Specific alterations in macrophage plasma membrane markers were observed in the annexin 1 null cells. Whereas no differences in dectin-1 and FcgammaR II/III expression were measured between the two genotypes, decreased membrane CD11b and F4/80 levels were measured selectively in macrophages lacking annexin 1. These cells also responded with an enhanced release of PGE(2) and COX-2 protein expression following addition of the soluble stimulants, LPS and heat-activated IgG. In conclusion, these results suggest that participation of endogenous annexin 1 during zymosan phagocytosis is critical and that this protein plays a tonic inhibitory role during macrophage activation.

Animals↗