Biomedical subjects

S Jancar

Publications and source records attributed to S Jancar.

At least 37 records · Page 2Linked to original sources

PubMed1998

Impairment in connective tissue mast cells degranulation in spontaneously hypertensive rats: stimulus dependent resistance.

1. Microvascular permeability in the mesentery and consequent leakage of protein into the peritoneum of spontaneously hypertensive rats (SHR) and normotensive rats (NTR) was measured in vivo by the extravasation of Evans blue dye. 2. In sensitized NTR, challenge with antigen produced extensive increases in dye extravasation in the mesentery and in peritoneal lavage fluid within 10 min. 3. In sensitized SHR there was no increase in the permeability of the mesentery and a very weak increase in dye extravasation in the peritoneal cavity following challenge. 4. The glucocorticoid antagonist RU38486 did not change the permeability response induced by antigen in sensitized NTR and SHR. 5. However, compound 48/80 was equally effective in either NTR or SHR in causing increased vasopermeability. 6. Mesenteric mast cells in the NTR were degranulated after immunological challenge, whereas those in the SHR were resistant, as measured histologically. 7. Similarly, challenge ex vivo of mesentery from sensitized NTR induced contraction of guinea-pig ileum in co-incubation experiments, whereas SHR mesentery was unresponsive. 8. Plasma levels of antigen-specific IgE and IgG2a in sensitized NTR and SHR were identical. 9. Immune serum from SHR was unable to induce a passive cutaneous anaphylaxis (PCA) reaction in the skin of NTR and SHR did not develop a PCA reaction upon passive sensitization with NTR immune serum. 10. We conclude that the mast cells of SHR are resistant to degranulation following immunological challenge, although the relevant antibodies are present.

Animals↗

PubMed1998

Thioglycollate-elicited murine macrophages are cytotoxic to Mycoplasma arginini-infected YAC-1 tumor cells.

Macrophages are important components of natural immunity involved in inhibition of tumor growth and destruction of tumor cells. It is known that these cells can be activated for tumoricidal activity by lymphokines and bacterial products. We investigated whether YAC-1 tumor cells infected with Mycoplasma arginini stimulate nitric oxide (NO) release and macrophage cytotoxic activity. Thioglycollate-elicited macrophages from male BALB/c mice were co-cultured for 20 h with YAC-1 tumor cells infected or not with Mycoplasma arginini. The cytotoxic activity was evaluated by MTT assay and nitrite levels were determined with the Griess reagent. Thioglycollate-elicited macrophages co-cultured with noninfected YAC-1 cells showed low cytotoxic activity (34.7 +/- 8.6%) and low production of NO (4.7 +/- 3.1 microM NO2-). These macrophages co-cultured with mycoplasma-infected YAC-1 cells showed significantly higher cytotoxic activity (61.4 +/- 9.1%; P < 0.05) and higher NO production (48.5 +/- 13 microM NO2-; P < 0.05). Addition of L-NAME (10 mM), an inhibitor of NO synthesis, to these co-cultures reduced the cytotoxic activity to 37.4 +/- 2% (P < 0.05) and NO production to 3 +/- 4 microM NO2- (P < 0.05). The present data show that Mycoplasma arginini is able to induce macrophage cytotoxic activity and that this activity is partially mediated by NO.

Animals↗

PubMed1997

A new murine model of pulmonary eosinophilic hypersensitivity: contribution to experimental asthma.

BACKGROUND: We have recently described a model of hypersensitivity reaction in the mouse paw, which induces a typical late-phase reaction with a marked eosinophilic infiltrate. OBJECTIVE: In the search for a murine model of asthma, this model was adapted to the lungs and compared with other models of pulmonary hypersensitivity. METHODS: A fragment of heat-coagulated hen's egg white was implanted subcutaneously, and 14 days later, the mice were challenged intratracheally with aggregated ovalbumin. Comparison was made with a group that received subcutaneous injection of soluble ovalbumin in alumen, challenged as described above and with four additional protocols of immunization and challenge. RESULTS: Forty-eight hours after challenge, the percentage of eosinophils was higher in the egg white implant group (35%) than in the group immunized with ovalbumin in alumen (10.4%). The eosinophil peroxidase activity in lung homogenates of the first group was also significantly higher (529 ng/ml) than that of the second group (43 ng/ml). These results were reproduced in five different mouse strains. Compared with five different models of lung hypersensitivity, the egg white implant model was unique in terms of persistence of the pulmonary eosinophilia. Histopathologic analysis of the lungs of mice immunized with egg white implant showed peribronchial, perivascular, and intraepithelial eosinophil infiltration; morphologic characteristics of bronchoconstriction; and patchy epithelial shedding. At 21 days, in addition to persistence of eosinophil infiltrate, enlarged alveoli, reflecting air trapping, were observed. CONCLUSION: On the basis of the characteristics of the model described here, we propose it as a suitable murine model of asthma.

Administration, Cutaneous↗

PubMed1997

PAF modulates eicosanoids and TNF release in immune-complex arthritis in rats.

The participation of lipid mediators and tumor necrosis factor (TNF) on an experimental model of immune-complex arthritis was investigated. Male Wistar rats received intraarticular injection of rabbit antibodies to bovine serum albumin into the knee joint followed by i.v. injection of the antigen. The levels of eicosanoids and TNF released into the synovial exudates were then assessed using ELISA and the L929 lytic cell assay, respectively. Increase in the levels of LTB4, TXB2 and PGE2 were detected 5 min, 5 min, and 6 h after arthritis induction, respectively. Pretreatment with the PAF receptor antagonist WEB 2170 decreased the levels of PGE2 and increased those of LTB4, without altering TXB2 levels. Increase in the levels of TNF was detected at 3 h of arthritis. Pretreatment with either the cycloxygenase inhibitor indomethacin or the 5-lipoxygenase inhibitor L-663,536 had no effect on TNF levels. Pretreatment with WEB 2170 significantly decreased TNF levels. These results are the first demonstration of eicosanoids and TNF release in immune-complex arthritis. The data also suggest that PAF had both a positive and negative modulatory role on the release of PGE2 and LTB4, respectively. Moreover, TNF release into the synovial exudate did not depend on eicosanoids whereas platelet activating factor (PAF) appeared to mediate the release of this cytokine in the model.

Animals↗

PubMed1997

A new murine model of persistent lung eosinophilic inflammation.

We summarize here the main characteristics of a novel model of pulmonary hypersensitivity. Mice were immunized with a subcutaneous implant of a fragment of heat solidified chicken egg white and 14 days later challenged with ovalbumin given either by aerosol or by intratracheal instillation. This procedure induces a persistent eosinophilic lung inflammation, a marked bone marrow eosinophilia, and Th2-type isotypic profile with histopathological findings that resemble human asthma. Further, this model is simple to perform, reproducible in different strains of mice, does not require adjuvants nor multiple boosters. Based on these characteristics we propose it as a suitable murine model of allergic eosinophilic lung inflammation.

Animals↗

PubMed1997

Malnutrition and experimental lung allergy.

BACKGROUND: Although it is commonly accepted that the immune response is affected by malnutrition there are very few data about its effect in allergic diseases. OBJECTIVE: The aim of the present study was to investigate the effect of malnutrition in allergic lung inflammation. METHODS: An anaphylactic reaction was induced in rat lungs and the increased vascular permeability was measured in the trachea, internal and external bronchi and parenchyma by the Evans blue extravasation method. These studies were conducted in two dietary groups: one fed a normoproteic diet (18%) and the other a hypoproteic diet (4.5%). When the animals were 60 days old the group fed the hypoproteic diet presented a reduction of 77.86% in bodyweight, 63.3% in food intake and 36% in plasma protein concentration characterizing a severe protein-calorie malnutrition. RESULTS: The anaphylactic reaction in the lungs induced a significant increase in vascular permeability in the trachea and bronchi of both dietary groups. However, the intensity of this effect was significantly lower in the malnourished group. Analysis of immunoglobulin isotypes in the serum by ELISA showed that whereas IgG1 and IgG2a levels were similar in both groups, the levels of IgE were significantly lower in the malnourished animals. Moreover, the levels of antigen-specific IgG1, IgG2a and IgE were all significantly inhibited by the protein-calorie malnutrition. When antibodies were passively transfered to the malnourished rats, they developed a reaction as intense as the normoproteic group. CONCLUSION: These results suggest that the capacity to release inflammatory mediators and the vascular response to these mediators is not affected by this type of malnutrition and, therefore, the diminished response of the airways reported here is probably due to the lower levels of anaphylactic antibodies produced by the malnourished rats.

Anaphylaxis↗

PubMed1995

Increased permeability of bovine aortic endothelial cell monolayers in response to a thromboxane A2-mimetic.

The present study was designed to investigate the ability of thromboxane to modulate the clearance rate of 125I-albumin through bovine aortic endothelial cell (BAEC) monolayer grown on polycarbonate micropore membrane. Stimulation of BAEC with the TXA2 mimetic U44069 (10(-8), 10(-7) and 10(-6) M) elicited a dose-dependent increase of labeled albumin passage across BAEC monolayers. This effect was markedly reduced by the TXA2 antagonist L655240 (10(-7) and 10(-6) M). Our results suggest that TXA2 may modulate the permeability of endothelial cells directly through activation of specific receptors.

Animals↗

PubMed1995

Effect of PAF antagonists on cerulein-induced pancreatitis.

The present study was undertaken to investigate the involvement of PAF in acute pancreatitis induced by cerulein in rats. Cerulein (two doses of 20 micrograms/rat, the first s.c. and the second i.v., 1 h apart) induced a significant increase in vascular permeability in the pancreas, evaluated by the Evans blue (EB) extravasation method. Plasma amylase levels were also significantly increased in this group. The PAF antagonists, BN-52021 (5 mg/kg) and WEB-2170 (1 and 10 mg/kg), both significantly reduced the extravasation of EB in the pancrease induced by i.v. injection of PAF (1 microgram/kg). At these concentrations, BN-52021 was effective at inhibiting cerulein-induced pancreatitis (60-70% of inhibition) whereas WEB-2170 had no significant effect. Although the inhibition induced by BN-52021 suggests the involvement of PAF in cerulein-pancreatitis, the lack of effect of WEB-2170 reported here does not allow a definite conclusion. Further studies are needed to elucidate the differential effect of the PAF antagonists.

Acute Disease↗

PubMed1995

Studies on the mechanism of PAF-induced vasopermeability in rat lungs.

The present study evaluated the effect of platelet activating factor (PAF) instilled into rat airways on vascular permeability assessed in isolated lung tissues by Evans blue (EB)-labelled plasma protein extravasation. It was found that intratracheal instillation of PAF induces a dose-dependent increase of EB extravasation in the bronchi (upper and inner) but not in the lung parenchyma. The contribution of eicosanoids to PAF-induced increase of vascular permeability was investigated by treating the animals with selected inhibitors prior to PAF administration. Mepacrine (5 mg/kg), L-663,536 (10 mg/kg), indomethacin (4 mg/kg) and dazoxiben (10 mg/kg) significantly reduced EB extravasation in the bronchi. The PAF antagonists BN-52021 (5 mg/kg), WEB-2086 (1 mg/kg), WEB-2170 (5 mg/kg) and PCA-4248 (3 mg/kg) were all effective in reducing the extravasation. These results suggest that PAF-induced increase of vascular permeability in rat bronchi is mediated by cyclooxygenase and lipoxygenase products of arachidonic acid metabolism.

Animals↗

PubMed1994

Hyperalgesia induced by Bothrops jararaca venom in rats: role of eicosanoids and platelet activating factor (PAF).

In this study we investigated the ability of Bothrops jararaca venom (BjV) to induce hyperalgesia and the modulation of this effect by lipid mediators. It was found that intraplantar injection of BjV (1 to 25 micrograms) caused a dose and time-related hyperalgesia. The peak of the hyperalgesic response was 1 hr after injection of the venom and persisted for 24 hr with the higher dose. The BjV-induced hyperalgesia was markedly attenuated by dexamethasone. Dexamethasone blocks the generation of biologically active metabolites from arachidonic acid by inhibiting PLA2 activation. Inhibition of the cyclo-oxygenase pathway by indomethacin, or inhibition of lipoxygenases by NDGA both significantly inhibited BjV-induced hyperalgesia. Two antagonists of PAF, WEB2170 and BN52021, also significantly inhibited the initial phase of the hyperalgesia. These results suggest that hyperalgesia induced by BjV is, at least partially, mediated by lipid mediators such as prostaglandins, leukotrienes and PAF.

Animals↗

PubMed1993

Platelet activating factor and histamine effects in synovial blood flow evaluated by laser-Doppler flowmetry.

OBJECTIVE: To investigate platelet activating factor (PAF) and histamine effects in synovial circulation of rabbits. METHODS: A laser-Doppler flowmeter was adapted to study the synovial blood flow. Either PAF or histamine were infused in the first femoral artery branch. The effects of PAF and histamine antagonists as well as of inhibitors of cyclooxygenase products were evaluated. RESULTS: PAF induced a vasoconstriction in synovial circulation, which was inhibited by the PAF antagonist, WEB 2170, a cyclooxygenase inhibitor, indomethacin or a thromboxane synthesis inhibitor, dazmegrel. Histamine induced vasoconstriction in the synovial vessels. Promethazine not only inhibited this vasoconstriction but also induced a vasodilation, that was blocked by a combined treatment with promethazine and cimetidine. Pretreatment with WEB 2170 did not interfere with histamine effect. CONCLUSIONS: Our data indicate that PAF induces vasoconstriction in synovial blood flow through a receptor mediated mechanism and that thromboxane is involved in this effect. Histamine induces constriction or dilation in synovial vessels, through action on H1 or H2 receptors, respectively. This effect is not dependent on PAF.

Animals↗

PubMed1993

Differential sensitivity of mouse strains to platelet activating factor-induced vasopermeability and mortality: effect of antagonists.

In the present study, we have compared the responses to platelet-activating factor (PAF) of A/J and BALB/c inbred mouse strains. Two PAF-induced events were analyzed: increased vasopermeability, measured by extravasation of Evans blue dye (EB), and mortality. PAF injected into the peritoneal cavity induced a bell-shaped dose-response curve of EB extravasation in both strains of mouse. In A/J mice, maximal EB extravasation was reached with 0.1 microgram of PAF/mouse, whereas in BALB/c mice maximal extravasation was attained at a 10-fold greater PAF concentration. PAF-induced mortality also differed among these mouse strains; the LD50 was 12.1 micrograms/kg in A/J and 21.2 micrograms/kg in BALB/c mice. Thus, these strains differ significantly regarding both events mediated by PAF. Surprisingly, the F1 hybrid (A/J x BALB/c) mice were as sensitive as the A/J strain to PAF-induced extravasation but were as resistant as the BALB/c mice to PAF-induced mortality. The effects of the PAF antagonists BN 52021 and WEB 2086 were compared in the F1 hybrids. It was found that 1.0 mg/kg of WEB 2086 affected PAF-induced extravasation at almost all PAF doses tested (0.03-3.0 micrograms) while 15 mg/kg of BN 52021 was only effective at doses of PAF below 0.3 microgram. Both antagonists prevented PAF-induced mortality. Our results indicate that the two events induced by PAF may be controlled by different genes.

Animals↗

PubMed1992

Immune-complex alveolitis in the rat: evidence for platelet activating factor and leukotrienes as mediators of the vascular lesions.

In the present study we investigated the involvement of lipid mediators in an experimental model of immune-complex alveolitis induced in rat lungs by intrabronchial instillation of rabbit antibodies to ovalbumin followed by i.v. injection of the antigen. It was found that the reaction did not induce detectable oedema, as measured by the dry:wet weight ratio. A marked influx of neutrophils was observed in the bronchoalveolar lavage fluid, progressing from 6 to 24 h in parallel with the development of haemorrhagic lesions in lung parenchyma. The intensity of these lesions, evaluated by the concentration of extravascular haemoglobin, was not significantly affected by pretreatment of the animals with a cyclo-oxygenase inhibitor (indomethacin), a thromboxane inhibitor (econazole) or a thromboxane antagonist (L-655,240). However, the antagonists of platelet activating factor (PAF), WEB-2086 and BN-52021, and the lipoxygenase inhibitors, nor-dihydroguaiaretic acid and L-663,536, all significantly inhibited the haemorrhagic lesions. A peptide leukotriene antagonist (L-660,711) had no effect. Furthermore, the PAF antagonists inhibited the levels of LTB4, but not of PGE2 and thromboxane, released into the bronchoalveolar space 1 h after induction of the reaction. These results suggest that the haemorrhagic lesions in this model of immune-complex alveolitis are mediated by PAF and leukotrienes, possibly LTB4.

Alveolitis, Extrinsic Allergic↗

PubMed1991

PAF induces rat plasma extravasation and releases eicosanoids during anaphylaxis.

The effects of anaphylaxis on vascular protein extravasation in selected tissues and on the release of prostaglandins in the peritoneal cavity were studied in sensitized rats. Extravasation of Evans blue dye was used as a measure of vascular permeability. Specific antigen challenge increased by 279, 297, 328, 250, and 192% the protein extravasation in the trachea, upper and lower bronchi, pancreas, and duodenum, respectively, but did not modify significantly the vascular permeability of the lung parenchyma, heart, liver, and kidney. Extravasation of Evans blue dye also was increased by 43-fold in the peritoneal cavity. Pretreatment of the animals with indomethacin (10 mg/kg) did not modify significantly the protein extravasation of the trachea, upper and lower bronchi, pancreas, and duodenum induced by anaphylaxis. Pretreatment with a mixture of mepyramine (3 mg/kg) and methysergide (2.5 mg/kg) reduced by 62, 66, and 40% the protein extravasation in the trachea, upper bronchi, and peritoneal cavity, respectively, in similar conditions. The PAF antagonist BN-52021 (5 mg/kg) very strongly reduced the protein extravasation elicited by anaphylaxis in the trachea, upper and lower bronchi, pancreas, and duodenum by 72, 87, 82, 67, and 85%, respectively, and by 53% in the peritoneal cavity. Anaphylaxis also increased the concentrations of thromboxane B2 and leukotriene B4 in the peritoneal exudates, but prostaglandin E2 levels were not affected. Pretreatment with BN-52021 reduced by 29 and 75% the level of thromboxane B2 and leukotriene B4 in the exudates. These results suggest that PAF, histamine, and serotonin mediate the protein extravasation associated with anaphylaxis, whereas prostaglandins are likely to play a minor role in this reaction.

Anaphylaxis↗

PubMed1991

Inhibitory effect of econazole on the release of thromboxanes.

The effect of econazole on the release of thromboxanes was investigated. It was found that econazole inhibited concentration-dependently the aggregation of guinea pig platelets stimulated with arachidonic acid. The compound also reduced significantly the LTB4-induced contraction of guinea pig lung parenchyma strips and the contraction of rabbit aorta to the effluent of LTD4-stimulated guinea pig lungs, both effects mediated mostly by thromboxane generation. The concentration of TXB2 in the effluents from LTD4 stimulated lungs, assayed by EIA, was significantly reduced following pretreatment of the lungs with 10(-4) M and 10(-5) M of econazole, whereas the levels of PGE2 were increased. These results demonstrate that econazole is a selective inhibitor of thromboxane synthesis.

Animals↗

PubMed1991

Mechanisms of thrombocytopenia in the acute phase of antigen-induced arthritis in rabbits.

Arthritis induced in hyperimmune rabbits by the intra-articular injection of the specific antigen was associated with a fall in circulating platelet number that lasted up to 60 days. Pretreatment of the animals with indomethacin and econazol at doses that significantly decreased thromboxane levels in the synovial fluids reduced the arthritis-related thrombocytopenia in the acute phase of arthritis. A similar inhibition was seen when L-655,240, a specific Thromboxane A2 antagonist, and BN 52021, a Platelet Activating Factor antagonist were used. The results suggest that both thromboxane and PAF are involved in the mechanisms leading to thrombocytopenia in this experimental model of arthritis.

Animals↗

PubMed1991

PAF antagonists do not modify IgE antibody production in mice.

The effect of selective PAF antagonists on the in vivo production of IgE antibodies was investigated. The anti-ovalbumin IgE antibody content was estimated by passive cutaneous anaphylactic reaction (PCA) in the plasma of Balb/c mice 10 days after immunization with ovalbumin and alum. The PAF antagonists, BN 52021 (5 mg/kg, ip), BN 50730 (20 mg/kg, po), WEB 2086 (2 mg/kg, ip) and WEB 2170 (5 mg/kg, ip) were administered 1 h before immunization and twice a day for 8 days thereafter. The effect of the antagonists on the PAF-induced vasopermeability was also assayed. In the immunized mice the level of antiovalbumin IgE antibody, estimated by PCA titer, was 1/640. The treatment with the PAF antagonists did not change this level. At the concentrations employed, the antagonists BN 50730, WEB 2086 and WEB 2170 significantly reduced the PAF-induced vascular permeability. These results suggest that PAF does not seem to have a relevant effect on the production of IgE antibodies in vivo in the system used in the present study.

Animals↗

PubMed1990

Studies on inflammatory response induced by Ehrlich tumor in mice peritoneal cavity.

In the present study we investigated the inflammatory response induced by the inoculation of Ehrlich tumor cells (EAT) into the peritoneal cavity of mice. It was found that after inoculation of 10(3) EAT cells, the number of peritoneal leukocytes remained unchanged till the sixth day. Subsequently, the number of cells increased as a consequence of tumor growth. EAT cells did not induce influx of PMN leukocytes till six days after tumor implantation, but a significant influx was observed on the tenth day. Inoculation of the tumor cells did not induce production of H2O2 by peritoneal cells at any time examined and induced low levels of macrophage spreading only until the third day after tumor implantation but not later on. The levels of thromboxane in the peritoneal cavity were not affected by the presence of the tumor, whereas prostaglandin E2 levels were significantly increased at all times examined. The biological significance of these results on the evolution and escape of the tumor from host defense mechanisms is under investigation.

Animals↗