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Biomedical subjects

B Ringertz

Publications and source records attributed to B Ringertz.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of an essential fatty acid-supplemented diet on leukotriene B4-induced rat neutrophil functions.

This study evaluated the effect of dietary supplementation with the essential fatty acid linoleic acid to 10% of the energy content of a diet on the stimulus-response coupling of rat peritoneal neutrophils. When stimulated with leukotriene B4 neutrophils from essential fatty acid supplemented rats responded with a significantly more pronounced oxidative metabolism (assessed as luminol augmented chemiluminescence) relative to control cells from rats on a normal 3% of total energy essential fatty acid diet. Chemiluminescence response to the formylpeptide N-formyl-norleucyl-leucyl-phenylalanine-norleucyl-thyrosyl-leucine was similarly enhanced. In contrast, responses elicited by the lectin concanavalin A did not differ between the two dietary groups. In response to leukotriene B4 a dose-related inhibition of neutrophil aggregation was observed, whereas chemotaxis did not differ between the two groups. Thus, linoleate supplementation is associated with a stimulus-specific modulation of neutrophil oxidative and aggregatory responses suggesting an effect on early, conceivably receptor-linked, steps of the stimulus-response coupling.

Animals↗
PubMed1991

Antirheumatic effects of fasting.

Total fasting induces within a few days a substantial reduction of joint pain, swelling, morning stiffness, and other arthritic symptoms in patients with rheumatoid arthritis. This remission subsides slowly after discontinuation of fasting. Its mechanisms are complex and involves diminished activation of neutrophils and lymphocytes and decreased generation of leukotrienes and of concentrations of serum complement factors, as well as of other proinflammatory systems. Moreover, ketosis and other metabolic and endocrine changes may be of significance for symptom expression and recognition.

Arthritis, Rheumatoid↗
PubMed1990

Effect of sulphasalazine and sulphapyridine on neutrophil superoxide production: role of cytosolic free calcium.

As the neutrophil granulocyte plays an important part in rheumatoid inflammation the effect of sulphasalazine on neutrophil function was studied. The results show that sulphasalazine, and its metabolite sulphapyridine, inhibit neutrophil superoxide production elicited by the receptor mediated stimulus N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) and by the calcium ionophore A23187. This effect seems to be dependent on inhibition of intracellular Ca++ increase as both substances reduce this increase upon cell activation with fMLP and A23187. Sulphasalazine and sulphapyridine do not inhibit superoxide production after stimulation with the ester phorbol myristate acetate, a stimulus response coupling which is independent of intracellular Ca++ increase. The reported inhibition of superoxide generation may explain, at least partly, the antirheumatic property of sulphasalazine.

Calcimycin↗
PubMed1990

Dietary linoleate supplementation modulates formyl-peptide receptor expression and functional responses of rat neutrophils.

We studied effects of dietary supplementation with the essential fatty acid (EFA) linoleic acid (LA) to see if neutrophil responses would be modulated. Neutrophils from rats maintained on a diet supplemented with EFA to 10% of the energy content--the high EFA (HEFA) group--showed a significantly higher LA concentration (but similar arachidonic acid content) compared with neutrophils from control rats maintained on a standard diet with 3% of the energy content as EFA. The HEFA group showed a significantly higher neutrophil oxidative metabolism compared with controls in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), but this response was equal to control values when stimulated by ionophore A23187, sodium fluoride, or phorbol myristate acetate. Similarly, FMLP conferred a more pronounced increase of intracellular Ca2+ in HEFA neutrophils, whereas this response to ionomycin was equal to that in controls. In contrast, HEFA rat neutrophil migration was decreased to 71% of the value in controls in response to FMLP. Similar results were observed for aggregation responses. On A23187 stimulation, HEFA and control neutrophils generated equal amounts of leukotriene B4 and other 5-lipoxygenase products as well as thromboxane B2 and 6-keto-prostaglandin F1 alpha. However, assessment of binding of FMLP labeled with tritium revealed an increase of the low affinity state of the FMLP receptor population. Thus an increased intake of one unsaturated fatty acid, LA, leading to its accumulation in neutrophils, conferred alterations in formyl-peptide-elicited responses, not associated with the formation of the assessed arachidonate-derived mediators, but most likely through the observed modulation of FMLP receptor subpopulations.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Substance P activates and modulates neutrophil oxidative metabolism and aggregation.

The substance P (SP) fragment SP(7-11) induced chemiluminescence (CL) and aggregation in human neutrophils at high concentrations (greater than or equal to 10 microM), whereas the entire molecule SP(1-11) was less potent and the SP(1-4) fragment was inactive. At these concentrations SP and its fragments also inhibited CL and aggregation evoked by subsequent addition of formyl-methionyl-leucyl-phenylalanine (fMLP), an effect that may depend on desensitization. However, at lower concentrations (1-10 nM) SP was able to prime human neutrophils to enhanced CL and enzyme release stimulated by fMLP. These findings indicate that, in addition to direct activation of CL and aggregation, SP also modulates neutrophil function and can thus amplify the release of potentially cytotoxic substances, a possible mechanism for nervous system involvement in rheumatoid arthritis.

Cell Aggregation↗
PubMed1988

Leukotriene B4 triggers highly characteristic and specific functional responses in neutrophils: studies of stimulus specific mechanisms.

By using human neutrophils we studied the on-off phenomenon for leukotriene B4 (LTB4) -induced functional responses compared with fMetLeuPhe (fMLP). LTB4 induced rapidly appearing and disappearing neutrophil chemiluminescent (CL), superoxide anion formation, aggregatory and membrane depolarizing responses, whereas fMLP responses were slower both in onset and termination. Increases of intracellular calcium concentrations (as reflected by quin2 and fura-2 fluorescence) were of similar magnitude for both stimuli; however, LTB4 responses were more rapidly terminated and fMLP responses were biphasic. When intracellular calcium fluxes, calmodulin or protein kinase C activities were inhibited by quin2, trifluoperazine, verapamil or 3,4,5-trimethoxybenzoic acid 8-diethylamino)octyl ester (TMB-8), profound changes were noted for chemiluminescent and aggregation kinetics induced by fMLP, whereas kinetics of LTB4 responses were less affected. When drugs were used to modulate cAMP levels, or to inhibit cyclo- and lipoxygenase metabolites of arachidonic acid, no effects on response kinetics were observed. Cytochalasin B both amplified and delayed responses although chemiluminescent responses to fMLP were amplified more than those to LTB4. Despite those effects cytochalasin B did not enhance peak fura-2 or quin2 responses to either fMLP or LTB4. Thus, LTB4 rapidly initiates functional responses in neutrophils, and stimulus-specific response patterns are already discernable during the mobilization of calcium, and can be modulated by interference with calcium-dependent reactions.

Aminoquinolines↗
PubMed1988

Effects of fasting on disease activity, neutrophil function, fatty acid composition, and leukotriene biosynthesis in patients with rheumatoid arthritis.

Fourteen patients with rheumatoid arthritis (RA) were studied before, during, and after a 1-week total fast. Disease activity decreased, as did the neutrophil release of lysozyme induced by the ionophore A23187. The ability of zymosan-activated RA patient serum to aggregate control neutrophils was reduced, together with serum concentrations of C3. The relative contents of arachidonic acid and eicosapentaenoic acid were increased in serum, platelets, and neutrophils, whereas levels of linoleic acid and linolenic acid were unchanged. Fasting also reduced the release of leukotriene B4 from neutrophils. We thus conclude that a reduced ability to generate cytotaxins, reduced release of enzyme, and reduced leukotriene formation from RA neutrophils, together with an altered fatty acid composition of membrane phospholipids, may be mechanisms for the decrease of inflammatory symptoms that results from fasting.

Adult↗
PubMed1988

Effects of lipoxins A and B on functional responses of human granulocytes.

The effects of synthetic lipoxin A and B (LXA and LXB) as well as several of their isomers were assessed as inducers of functional responses of human granulocytes. LXA stimulated migration at 1 nM and exhibited a variable effect as inducer of chemiluminescence at concentrations greater than or equal to 1 microM. Both migration and chemiluminescence evoked by LXA proved to be highly stereospecific, since e.g. 6S-LXA was less active than LXA. Neither synthetic LXA nor several of its stereoisomers provoked degranulation, aggregation, membrane potential changes or intracellular calcium fluxes. In addition, LXB and its isomers did not stimulate aggregation, degranulation or chemiluminescence. Pretreatment of granulocytes with LXA did not modify subsequent challenges with leukotriene B4. Together, these results indicate that granulocyte responses to LXA are highly stereospecific and are mediated by other mechanisms than those evoked by leukotriene B4.

Calcium↗
PubMed1988

Rat neutrophil function, and leukotriene generation in essential fatty acid deficiency.

Since the essential fatty acid linoleic acid is the precursor of arachidonic acid and thus of leukotrine B4 (LTB4), essential fatty acid deficiency (EFAD) may result in decreased synthesis of this stimulator of neutrophil granulocyte functions. Peritoneal and blood neutrophils from rats fed a diet with only 0.3% of energy requirements as linoleic acid and exhibiting biochemical evidence of EFAD showed substantial functional impairments compared to neutrophils from rats maintained on a diet with 3% of the energy requirement as linoleic acid. Oxidative burst activation (assessed by chemiluminescence), chemotaxis and aggregation were impaired upon stimulation with formylpeptides or the ionophore A23187. In contrast, these functions were intact on stimulation with exogenous LTB4. Chemiluminescence was slightly but not significantly enhanced in EFAD rat neutrophils compared to controls when stimulated with phorbol myristate acetate (PMA). There were no differences between EFAD and control peritoneal neutrophils in the number of f-met-leu-phe (fMLP) receptors, or in their affinity for the ligand, assessed with fML(3H)P. The fraction of responding cells also were similar, assessed with dichlorofluorescein diacetate fluorescence. Moreover, the endogeneous LTB4 production in response to A23187 or fMLP was decreased by 57.7% and 63.5%, respectively, in EFAD peritoneal neutrophils. Thus, EFAD was associated with reductions of LTB4 production and neutrophil responsiveness to A23187 and formylpeptides but not to LTB4 or PMA, which supports the hypothesis that endogeneous LTB4 may contribute to the activation of neutrophil functions involved in inflammation and host defense.

Animals↗
PubMed1988

Recombinant human leukocyte interferon modulates neutrophil function in vitro.

Recombinant human interferon-alpha 2 (rIFN-alpha A) was evaluated as a modulator of neutrophil functions. Neutrophils treated with rIFN-alpha A for 1 h in vitro showed reduced chemiluminescence (CL) and aggregation in response to phagocytosis. In contrast, when certain soluble stimuli [f-met-leu-phe (fMLP) or leukotriene B4] were used, rIFN-alpha A treatment conferred a doubling of CL. This was paralleled by a similar increase in superoxide anion production and a 56% increase of release of beta-glucuronidase and lysozyme. The NBT test showed that IFN treatment did not increase the number of responding neutrophils. However, there was a significant increase in the displaceable binding of fML[3H]P. Enzyme release, aggregation, and CL in response to other soluble stimuli, the ionophore A23187 and phorbol myristate acetate were unaffected by IFN treatment. Likewise, chemotaxis was not affected. Thus, phagocytosis-associated events and aggregation were hampered by rIFN-alpha A whereas secretory responses to receptor-dependent soluble stimuli were augmented. The mechanism for the latter is most likely dependent on the observed modulation of binding of fMLP to its receptor.

Cell Migration Inhibition↗
PubMed1987

The effects of lipoxin A and lipoxin B on functional responses of human granulocytes.

Lipoxin A and lipoxin B (LXA and LXB) are formed from arachidonic acid by leukocyte 5- and 15-lipoxygenases. We have assessed the effects of synthetic lipoxins on functional responses of human granulocytes. LXA stimulated migration at 1 nM. The effect was highly stereospecific, since e.g. 6S-LXA and LXB were less active than LXA. Neither synthetic LXA nor several of its stereoisomers provoked degranulation or aggregation. LXB and its isomers did not induce any of these functional responses. These results indicate that migratory granulocyte responses to LXA are highly stereospecific.

Cell Aggregation↗
PubMed1986

Essential fatty acid deficiency in rats: effects on arachidonate metabolism, generation of cyclooxygenase products and functional responses in neutrophils.

Linoleic and arachidonic acid concentrations in neutrophils from rats maintained on a diet with only 0.3% of the energy content as essential fatty acid (EFA, EFAD group) were reduced by 70 +/- 2.2% and 34.8 +/- 5.2%, respectively, compared with controls fed a diet with a normal 3% EFA content. Neutrophil chemiluminescence and aggregation induced by f-Met-Leu-Phe was substantially reduced in the EFAD group. Production of 6-keto-prostaglandin F1 alpha and thromboxane B2 were significantly lower in the EFAD neutrophils when stimulated by the ionophore A23187, whereas there was no difference when leukotriene B4 was used as stimulus.

Animals↗
PubMed1986

Neutrophil aggregation--factors modulating stimulus-specific responses.

After stimulation with various soluble stimuli, e.g. fMLP and LTB4, human neutrophils aggregated in a characteristic and stimulus-specific way. They formed clumps of cells, mainly pairs and triplets. Their calculated total light-obscuring cell area corresponded well with the recorded aggregation response assessed as light transmittance, when not only neutrophil clumping but also cell swelling and shape changes were taken into account. Changes of neutrophil concentrations had only marginal effects on maximal responses and their kinetics. Lowering cell temperature to 26 degrees C decreased the responses to fMLP, whereas LTB4 responses were more inhibited by increasing temperatures to 42 degrees C. At 26 degrees C, both LTB4 and fMLP induced biphasic aggregation waves with two peaks. Cytochalasin B enhanced the response both to LTB4 and fMLP, and LTB4 responses became biphasic with an early peak preceding the major response. The presence of high concentrations of platelets potentiated aggregation responses, a phenomenon that could not be ascribed to generation of cyclo-oxygenase products. Thus, the formation of neutrophil aggregates and the subsequent change in light transmission can be modulated by several experimental factors which influence the stimulus-specific responses, and the effects on fMLP-induced aggregation under some experimental conditions are different from those on LTB4.

Blood Platelets↗
PubMed1985

Stimulus-specific neutrophil aggregation: evaluation of possible mechanisms for the stimulus-response apparatus.

We have assessed the effects of formyl peptides, leukotrienes, zymosan-activated serum (ZAS), and calcium ionophore A 23187 on the aggregation response of human neutrophils to characterize the mechanisms involved, particularly the possible contribution of the concomitant burst of oxidative metabolism and degranulation. We found that the tested stimuli induced aggregation waves highly characteristic for each agent. With formyl peptides, such as f-Met-Leu-Phe (fMLP), f-Met-Met-Met-Met (fMMMM), and f-Nle-Leu-Phe-Nle-Tyr-Leu (fNLPNTL), peaks appeared after greater than 60 seconds and were followed by a slow disaggregation. In contrast, leukotriene B4 (LTB4) and its omega-oxidized metabolites, 20-OH-LTB4 and 20-COOH-LTB4, induced rapidly occurring peaks that were maximal after 15 to 30 seconds and that were followed by a rapid and marked disaggregation. ZAS induced peak values after 30 to 90 seconds, and disaggregation kinetics were between fMLP and LTB4. A 23187 in high concentrations (10 to 50 mumol/L) elicited biphasic aggregation waves, whereas lower concentrations induced less pronounced and continuous aggregation responses. Superoxide dismutase, catalase, mannitol, and Tiron did not influence any of the aggregation characteristics. Colchicine and indomethacin did have some effects on peak values but not on the characteristic curve profiles, whereas cytochalasin B had a profound effect on the aggregation response for all tested stimuli. Neutrophils from a patient with chronic granulomatous disease exhibited aggregation responses similar to those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcimycin↗