PubMed Health⌕ Search

Biomedical subjects

F P Nijkamp

Publications and source records attributed to F P Nijkamp.

At least 19 recordsLinked to original sources
PubMed1992

Virus-induced airway hyperresponsiveness in guinea pigs in vivo: study of broncho-alveolar cell number and activity.

Recently, we demonstrated that an increased airway responsiveness in vitro can be measured 4, 8, and 16 days, but not 2 days, after intratracheal inoculation of parainfluenza-3 (PI-3) virus to guinea pigs. In the present study airway responsiveness was measured in vivo, and the number, types and activity of broncho-alveolar cells was determined. A significant increase in airflow resistance was measured in spontaneously breathing anesthetized guinea pigs in response to histamine and methacholine, 4 and 8 days after PI-3 virus inoculation. 2 days after inoculation with control solution or PI-3 virus, no difference in the total number of inflammatory cells was observed in the broncho-alveolar lavage fluid. In contrast, on days 4, 8, and 16 after infection a significant increase in the number of alveolar macrophages (102%, 76%, 68%, respectively), monocytes (552%, 374%, 360%, respectively), and lymphocytes (253%, 675%, 396%, respectively) was found. The number of eosinophils was increased as well, but faded with time (378%, 312%, 63%, respectively). PI-3 virus was found to be a very potent activator of broncho-alveolar cells as measured by chemiluminescence. The increase in chemiluminescence production in response to PI-3 virus was reduced in cells obtained from PI-3 virus pretreated animals (day 2, 42%; day 4, 65%; day 8, 22%; and day 16, 30%). In conclusion, PI-3 virus can stimulate broncho-alveolar cells and the virus-induced airway hyperresponsiveness is associated with an influx of inflammatory cells in the respiratory tract.

Airway Resistance↗
PubMed1992

Viral infection in guinea pigs induces a sustained non-specific airway hyperresponsiveness and morphological changes of the respiratory tract.

In the present study an animal model is described in which a sustained non-specific airway hyperresponsiveness is induced. Guinea pigs were inoculated intratracheally with parainfluenza type 3 (PI-3) virus or control solution. Two, 4, 8, and 16 days after inoculation the tracheae, bronchi, and lung strips were isolated and mounted in organ baths. Two days after inoculation no difference between the control solution and PI-3 virus group was observed, with respect to the histamine concentration/response curve obtained from tracheae, bronchi and lung strips of the respective groups. However, histamine concentration/response curves were significantly (P less than 0.01) shifted upwards in all parts of the airways 4, 8, and 16 days after PI-3 inoculation as compared with the control solution. The excessive contraction of the trachea was not specific for histamine, since an increase in the maximal response was obtained also for the cholinergic receptor agonist, arecoline on day 4 (32%, P less than 0.05), day 8 (24%, P less than 0.05), and day 16 (28%). Morphological examination of the central airways obtained from control solution-inoculated animals revealed no signs of inflammation. However, 2, 4, and 8 days, but not 16 days, after the viral infection, epithelial damage with loss of cilia and mucus-depleted goblet cells were observed. Thus, morphological changes were not directly associated with changes in airway responsiveness. Histological examination of the peripheral airways revealed an influx of inflammatory cells, as shown by typical lesions of patchy alveolitis and bronchiolitis. Bronchiolar epithelium was variously hyperplastic and dysplastic with degenerative changes, and the lumens of the bronchioli were occluded with mucus and inflammatory cells. In conclusion, the virus-induced airway hyperresponsiveness in guinea pigs shows similarities with the human situation, in which a sustained non-specific airway hyperresponsiveness is observed after a respiratory viral infection. In addition, the hyperresponsiveness seems to be accompanied by an influx of inflammatory cells in the airways but not with other morphological changes.

Animals↗
PubMed1992

13-hydroxyoctadecadienoic acid attenuates oedema formation induced by leukotriene B4 in vivo in rabbit skin.

Intradermal 13-hydroxyoctadecadienoic acid (13-HODE; 10(-11)-10(-9) mol/site) inhibited oedema formation induced by the neutrophil-dependent mediator leukotriene B4 (LTB4) in the presence of calcitonin gene-related peptide (CGRP; 10(-11) mol/site) in rabbit skin. In contrast, the responses to the direct acting mediators bradykinin and histamine were unaffected by 13-HODE. 13-HODE failed to induce oedema formation in rabbit skin when injected alone or in the presence of the potent vasodilator CGRP. These results present a novel interaction between 13-HODE and LTB4 that could have important implications in the pathogenesis of inflammation.

Analysis of Variance↗
PubMed1992

Effect of albumin on adenylate cyclase receptor-related signal transduction of human peripheral blood mononuclear cells.

In the present study we investigated in vitro the effect of human serum albumin (HSA) on receptor-stimulated cAMP production in isolated human peripheral blood mononuclear cells (PBMC). The cAMP production is strongly correlated with the pH of the medium during long incubations with albumin. Adenylate cyclase is stimulated by receptor agonists like histamine, forskolin, prostaglandin E2 and the beta-adrenergic agonist isoprenaline, in the presence or absence of HSA. This protein, at concentrations above 0.1%, dose-dependently inhibits both basal and agonist-stimulated cAMP levels in PBMC. In the presence of 0.5% HSA a significant reduction of 30-60% (cell batch dependent) is induced, a reduction which is not incubation time dependent. Washing the cells after a period of incubation with 2% HSA does not reverse the HSA-induced cAMP inhibition. Oleic acid-evoked conformational changes in HSA were not capable of influencing the inhibition processes of HSA on the isoprenaline-stimulated cAMP production. Structure-controlled interactions between HSA and membrane or adenylate cyclase are therefore unlikely. Bovine serum albumin and chicken albumin had different effects upon the agonist-stimulated cAMP production as compared with HSA. At this moment no explanation for this behavior can be provided. The findings indicate that albumin may inhibit non-specifically cAMP production in PBMC and possibly influences membrane-controlled processes.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Effects of apocynin, a drug isolated from the roots of Picrorhiza kurroa, on arachidonic acid metabolism.

Apocynin is a constituent of root extracts of the medicinal herb Picrorhiza kurroa and has been shown to possess anti-inflammatory properties. We investigated the effects of apocynin on the production of arachidonic acid-derived inflammatory mediators by guinea pig pulmonary macrophages. Apocynin concentration-dependently inhibited the formation of thromboxane A2, whereas the release of prostaglandins E2 and F2 alpha was stimulated. Apocynin potently inhibited arachidonic acid-induced aggregation of bovine platelets, possibly through inhibition of thromboxane formation. The present results suggest that apocynin might, beside its therapeutic effects in inflammatory conditions when given in a root extract of P. kurroa, also be a valuable tool in the development of new anti-inflammatory or anti-thrombic drugs.

Acetophenones↗
PubMed1992

Effects of cytokines on beta-adrenoceptor function of human peripheral blood mononuclear cells and guinea pig trachea.

In asthma, a beta-adrenoceptor dysfunction may be the consequence of an active disease state rather than a fundamental abnormality. In the present study the possible involvement of T lymphocytes in beta-adrenergic impairment was investigated by studying the effects of lymphocyte-derived mediators of beta-adrenoceptor function of human peripheral blood mononuclear cells (PBMCs) and guinea pig trachea. Supernatants of phytohemagglutinin- or concanavalin A-activated PBMCs from either persons with asthma or healthy persons inhibited isoprenaline stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production of PBMCs after 20 hours of preincubation. These supernatants also inhibited beta-adrenoceptor function of PBMCs from patients with asthma to the same extent. The isoprenaline stimulated cAMP production of PBMCs was not altered after a 2-hour preincubation period with human interleukin-1 (IL-1), IL-2, IL-3, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN-gamma). In contrast, after 20 hours of preincubation, stimulated cAMP production of PBMCs was significantly diminished, with 63% by IL-1 (40 U/ml, p less than 0.01), with 36% by IL-2 (100 U/ml, p less than 0.05), with 37% by IFN-gamma (1000 U/ml, p less than 0.05), and with 21% by GM-CSF (100 U/ml, p less than 0.05). Preincubation of guinea pig tracheal segments with IL-1, IL-2, IL-4, or GM-CSF during 1 or 3 days did not affect the EC50 values or the maximal relaxation of isoprenaline dose response curves.

Animals↗
PubMed1992

Virus-induced airway hyperresponsiveness in the guinea pig can be transferred by bronchoalveolar cells.

For the investigation of whether inflammatory cells were responsible for virus-induced airway hyperresponsiveness, tracheal spirals from healthy guinea pigs were incubated in organ baths with different numbers of bronchoalveolar cells obtained from guinea pigs 4 days after their inoculation with parainfluenza-3 (P-3) virus or control solution. Airway responsiveness was measured by performance of histamine concentration/response (C/R) curves on the tissues. Preparations incubated with 5 x 10(5) cells/ml obtained from guinea pigs treated with P-3 virus demonstrated a significant upward shift of the histamine C/R curve. The maximal contraction was increased by 26% as compared with the tissues incubated with the same number of cells from animals inoculated with control solution. When the number of cells was increased further to 5 x 10(6) cells/ml, no additional upward shift of the C/R curve was seen; the increase in maximal contraction was 24%. Tracheal spirals incubated with 5 x 10(4) cells/ml did not affect the histamine C/R curves. Addition of P-3 virus to the organ bath during the incubation period with the cells did not affect the histamine C/R curve either, irrespective of the inoculation solution or the number of bronchoalveolar cells used. The relative number of alveolar macrophages in bronchoalveolar lavage fluid decreased significantly from 86.3% +/- 2.6% in the control group to 71.8% +/- 3.3% in the P-3 virus group as a consequence of a significant increase in the percentage of monocytes, lymphocytes, and eosinophils. These results suggest that bronchoalveolar cells are causally involved in the virus-induced airway hyperresponsiveness.

Animals↗
PubMed1992

Bovine polymorphonuclear leukocytes increase sensitivity to noradrenaline in isolated mesenteric arteries.

1. The effects of polymorphonuclear leukocytes (PMN) on vascular function to (-)-noradrenaline were examined in vitro. Purified bovine PMN were incubated in siliconized organ baths containing rings of bovine mesenteric arteries, after which a concentration-effect curve in response to (-)-noradrenaline was obtained. 2. PMN-derived products induced a long lasting concentration-dependent contraction of the blood vessels generating 24.4 +/- 6.8% of the maximal tension to (-)-noradrenaline at a cell concentration of 2.5 x 10(6) ml-1. The contractile response was also found in endothelium-denuded vascular rings. 3. PMN present in the organ bath caused an increase in the sensitivity of vascular rings to (-)-noradrenaline. At a cell number of 2.5 x 10(6) PMN ml-1 the pD2-value for (-)-noradrenaline was augmented 0.40 +/- 0.05 (P less than 0.001), while total contraction at the highest concentration (-)-noradrenaline was not affected. This increase in sensitivity was dependent on an intact endothelium. 4. The increase in sensitivity to (-)-noradrenaline by PMN was inhibited by superoxide dismutase, but not by catalase, dimethylthiourea, indomethacin or nordihydroguaiaretic acid. The non-stimulated bovine PMN produced oxygen radicals as measured by chemiluminescence. 5. Simultaneous incubation of PMN and (-)-noradrenaline with arterial rings induced an increase in the release of prostacyclin, measured by an elevated concentration of 6-keto-prostaglandin F1 alpha in the supernatant. 6. It is concluded that PMN can increase vascular tone directly or indirectly probably via the interaction of PMN-derived superoxide anions with endothelium-derived relaxing factor.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Determination of alpha 1-adrenoceptor subtype selectivity by [3H]-prazosin displacement studies in guinea-pig cerebral cortex and rat spleen membranes.

1. [3H]-prazosin homogeneously labels alpha 1-adrenoceptors in guinea-pig cerebral cortex and rat spleen membranes with dissociation constants of 1.28 and 1.49 x 10(-10) M respectively. 2. Phentolamine and WB 4101 displacement studies show that guinea-pig cerebral cortex contains 30% alpha 1A- and 70% alpha 1B-adrenoceptor subtypes, whereas rat spleen contains a virtually homogeneous alpha 1B-adrenoceptor subtype population. The alpha 1-adrenoceptor population of rat thoracic aorta is predominantly of the alpha 1A-adrenoceptor subtype, and in guinea-pig thoracic aorta it is mainly of the alpha 1B-adrenoceptor subtype. 3. Half of the compounds displacing [3H]-prazosin bound to guinea-pig cerebral cortex membranes display alpha 1A-adrenoceptor selectivity. Among these compounds, WB 4101 and methoxamine are most selective, displaying selectivity ratios of approximately 38 and approximately 26 respectively. 4. The affinity constants of the non-selective compounds for the alpha 1-adrenoceptor in guinea-pig cerebral cortex membranes correlate well with the affinity constants obtained for alpha 1B-adrenoceptors in rat spleen membranes. The affinities of selective compounds for the alpha 1B-adrenoceptor subtype in guinea-pig cerebral cortex correlate very well with their affinity for alpha 1B-adrenoceptor in the rat spleen homogenate. Both regression lines coincide with the line of identity. The affinity constants of selective compounds for the alpha 1A-adrenoceptors in guinea-pig cerebral cortex only apparently correlate with the affinity for either the alpha 1B-adrenoceptors in guinea-pig cerebral cortex or in the rat spleen. Regression analyses indicate a straight line relationship (r2>0.9) between pKEA and Pk1B but the regression lines deviate from the line of identity.

Adrenergic alpha-Agonists↗
PubMed1992

Pasteurella haemolytica leukotoxin enhances production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by bovine polymorphonuclear leukocytes.

The influence of the leukotoxin of Pasteurella haemolytica on the generation of arachidonic acid metabolites by bovine polymorphonuclear leukocytes (PMNs) was investigated. PMNs released 5-, 12-, and 15-hydroxyeicosatetraenoic acids (5-, 12-, and 15-HETE) and leukotriene B4 (LTB4) upon stimulation with arachidonic acid. The leukotoxin preparations dose dependently enhanced the release of the 5-lipoxygenase products 5-HETE and LTB4 in arachidonic acid-stimulated PMNs, whereas the release of 12- and 15-HETE was not affected. The enhanced release of LTB4 and 5-HETE was not due to a decreased cellular retention of the 5-lipoxygenase products. In addition, leukotoxin preparations by themselves were also able to induce LTB4 and 5-HETE production in the absence of exogenous arachidonic acid. Generation of 5-lipoxygenase products by PMNs stimulated by leukotoxin may represent an important cellular event that occurs during infections with P. haemolytica.

Animals↗
PubMed1991

5-HT1-like receptors mediate potentiation of cholinergic nerve-mediated contraction of isolated mouse trachea.

While it had no effect on the resting tension of mouse tracheal segments, 5-HT (10(-8)-10(-4) M) potentiated concentration dependently the contractions induced by electrical field stimulation (EFS). The maximal potentiation was 105 +/- 38% and the EC50 value was 1.4 +/- 0.6 x 10(-6) M (n = 6). The responsiveness of mouse trachea to acetylcholine was not altered by 5-HT (10(-5) M). The 5-HT1A,B antagonist pindolol (10(-6) M), the combined 5-HT2 and 5-HT1C receptor antagonist, ketanserin (10(-6) M), or the combined 5-HT1 and 5-HT2 receptor antagonist, methysergide (10(-6) M), all partially inhibited the effect of 5-HT on the twitch responses. Blockade of 5-HT3 receptors by GR 38032F (10(-6) M) did not affect the potentiation by 5-HT. Antagonism of 5-HT3 and 5-HT4 receptors by ICS 205,930 (3 x 10(-6) M) increased the potentiation of the twitch responses by 5-HT, this was probably due to a decrease of the baseline EFS-induced twitch response by ICS 205,930. Alkylation of the 5-HT2 receptor by phenoxybenzamine (3 x 10(-7) M) treatment did not significantly affect the potentiation of the twitch responses by 5-HT. The beta-adrenoceptor antagonist, timolol (10(-6) M), and the alpha-adrenoceptor antagonist, phentolamine (10(-6) M), did not influence the potentiation of the twitch responses by 5-HT, excluding the involvement of the adrenergic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

Effect of cyclosporin-A treatment on endotoxin-induced airway hyperreactivity in vivo and in vitro in guinea-pigs.

In the present study, the role of T-lymphocytes in the development of histaminergic hyperreactivity of the airways in vivo and in vitro, after intraperitoneal administration of bacterial endotoxin (1 mg/kg) to guinea-pigs was examined. Daily oral administration of the T-lymphocyte-selective immunosuppressive drug cyclosporin A (25 mg/kg) did not prevent the endotoxin-induced airway hyperreactivity in vivo. Cyclosporin A treatment itself induced histaminergic hyperreactivity of guinea-pig trachea in vitro. In cyclosporin A-pretreated guinea-pigs, endotoxin did not further potentiate the histaminergic responsiveness of isolated tracheal spirals. It can be concluded that T-lymphocytes do not play a role in the endotoxin-induced airway hyperreactivity in vivo. Furthermore, no definite conclusion concerning the involvement of T-lymphocytes in the endotoxin-induced hyperreactivity in vitro can yet be drawn.

Animals↗
PubMed1991

Production of arachidonic acid and linoleic acid metabolites by human bronchoalveolar lavage cells.

Fatty acid-derived inflammatory mediators are considered to play an important role in airway hyperresponsiveness of asthmatic patients. The pulmonary macrophage may be an important source for these mediators in airway tissue. We investigated the metabolism of arachidonic acid and linoleic acid by human bronchoalveolar lavage cells, mainly comprising pulmonary macrophages. Arachidonic was mainly metabolized by 5-lipoxygenase, giving rise to the formation of leukotriene B4 and 5-hydroxy-eicosatetraenoic acid (5-HETE). Linoleic acid was converted to 5 major metabolites, including the 9-hydroxy and 13-hydroxy derivatives, 9- and 13-hydroxy-octadecadienoic acid (9- and 13-HODE). The formation of HODEs could be inhibited by cyclooxygenase inhibitors as well as lipoxygenase inhibitors, indicating that both enzymic species play a role in the generation of HODEs.

Arachidonate 5-Lipoxygenase↗
PubMed1991

9- and 13-hydroxy-linoleic acid possess chemotactic activity for bovine and human polymorphonuclear leukocytes.

The presence of polymorphonuclear leukocytes (PMNs) within the airways is a characteristic feature of a variety of lung diseases. Pulmonary alveolar macrophages (PAMs) and epithelial cells release many different factors which contribute to the recruitment of inflammatory cells into infected airways. PAMs and tracheal epithelial cells are able to produce linoleic acid metabolites (9-HODE and 13-HODE) besides arachidonic acid metabolites. The objective of the present study was to determine whether 9-HODE and 13-HODE possess chemotactic activity for isolated PMNs. It was found that 9-HODE and 13-HODE induced a chemotactic response of both human and bovine PMNs in vitro. The HODEs evoked chemotaxis with a linear dose response from 10(-10) to 10(-6) M to the same extent as the arachidonic acid metabolite 15-HETE. At 10(-8) M, 9-HODE and 13-HODE were approximately half as potent in inducing chemotaxis as compared to LTB4.

Animals↗