Consumption of plant extract supplement reduces platelet activating factor-induced platelet aggregation and increases platelet activating factor catabolism: a randomised, double-blind and placebo-controlled trial.

Platelet-activating factor (PAF) is a potent mediator of inflammation that plays a crucial role in atherosclerosis. The purpose of this study was to evaluate the effect of a dietary supplement containing mainly plant extracts on PAF actions and metabolism in healthy volunteers. A double-blind, placebo-controlled, 8 weeks' duration study was performed. Healthy volunteers were randomly allocated into the supplement or the placebo group and fifty-eight of them completed the study. The supplement contained plant extracts (Aloe gel, grape juice, Polygonum cuspidatum) and vitamins. The activities of PAF metabolic enzymes: the two isoforms of acetyl-CoA:lyso-PAF acetyltransferase, cytidine 5'-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-cholinephosphotransferase) and platelet-activating factor-acetylhydrolase (PAF-AH) in leucocytes and lipoprotein associated phospholipase-A2 in plasma were measured along with several markers of endothelial function. Platelet aggregation against PAF, ADP and thrombin receptor activating peptide was measured in human platelet-rich plasma by light transmission aggregometry. No difference was observed on soluble vascular cell adhesion molecule-1, sP-selectin and IL-6 levels at the beginning or during the study period between the two groups. Concerning PAF metabolism enzymes' activity, no difference was observed at baseline between the groups. PAF-AH activity was only increased in the supplement group at 4 and 8 weeks compared with baseline levels. In addition, supplement consumption led to lower platelet sensitivity against PAF and ADP compared with baseline levels. However, a trial effect was only observed when platelets were stimulated by PAF. In conclusion, supplementation with plant extracts and vitamins ameliorates platelet aggregation primarily against PAF and secondarily against ADP and affects PAF catabolism by enhancing PAF-acetylhydrolase activity in healthy subjects.

[ON THE ISSUE OF SELECTION OF COAGULANTS UNDER ADP-INDUCED IMPEDANCE TEST OF AGGREGATION OF THROMBOCYTES IN PATIENTS WITH CHRONIC MYELO-PROLIFERATIVE TUMORS].

The evaluation was implemented concerning impact of anticoagulants used during venous blood sampling, on aggregation of thrombocytes and acetylsalicylic acid effect in vitro in 111 patients with suspicion to chronic myelo-proliferative tumors and 16 healthy volunteers. The vacutainers (Becton Dickinson) with 3.2% citrate, with heparin (Becton Dickinson) and S-Monovette system (Sarstedt AG & Co) with recombinant herudin were applied. The analysis of aggregation was implemented using the technique of impedance in whole blood before and after preliminary incubation of blood samples with acetylsalicylic acid effect in 0.1 mM concentration. The induction was implemented by ATP in final concentration of 5 mkM. It is demonstrated that ATP-induced amplitude of aggregation under application of heparin and hirudin is significantly higher in comparison with its level in samples of citrate blood. At that, acetylsalicylic acid effect paradoxically increases amplitude of aggregation in samples with heparin but not in samples with citrate or hirudin. The application of hirudin permits evaluating impact of acetylsalicylic acid effect both at aggregation and disaggregation component of thrombocyte functions under erythrocytosis and thrombocytosis and can be recommended as a preferable approach in testing individual sensitivity of patients to acetylsalicylic acid effect.

[Changes of prostaglandin D2,carboxypeptidase A3 and platelet activating factor in guinea pig in anaphylactic shock].

OBJECTIVE: To detect the changes of leukotriene E4(LTE4), prostaglandin D2(PGD2), carboxypeptidase A3(CPA3) and platelet activating factor (PAF) in guinea pigs died from anaphylactic shock. METHODS: Guinea pigs were used for establishing anaphylactic shock models. The levels of LTE4, PGD2 and CPA3, and PAF were detected in urine, plasma, and brain tissues with ELISA kit, respectively. The significant biomarkers were selected comparing with control group. The changes of PGD2, CPA3 and PAF in the guinea pigs at time zero, 12 and 24 hours after death were observed and compared respectively. The effect of platelet activating factor acetylhydrolase (PAF-AH) to PAF in guinea pig brain was examined and compared. RESULTS: There were no statistically differences of LTE4 levels in urine observed between experimental group and control group. The levels of CPA3, PGD2 and PAF in the experimental group were significantly higher than that in the control group at 0 h. The levels of PAF at 12 and 24 hours after anaphylactic shock were significantly higher than that in the control group. The levels of PAF decreased significantly after pretreatment with PAF-AH. CONCLUSION: LTE4 in urine cannot be selected as a biomarker to determine the anaphylactic shock. PGD2 and CPA3 in plasma, and PAF in brain tissue may be used as biomarkers to determine the anaphylactic shock. PAF-AH may be potentially useful for clinical treatment of anaphylactic shock.

Dimeric prenylated C6-C3 compounds from the stem bark of Illicium oligandrum.

Three new dimeric prenylated C6-C3 compounds, namely, illicidiones A (1), B (2), and C (3), were isolated from the stem bark of Illicium oligandrum. The structure and absolute configuration of these compounds were determined by extensive spectroscopic and chemical analyses, including NMR, modified Mosher method, and single-crystal X-ray study. Compounds 1-3 exhibited weak anti-inflammatory activities.

Two new ginkgolides from the leaves of Ginkgo biloba.

Two new diterpenoid compounds, ginkgolide P(1) and ginkgolide Q(2), were isolated from the leaves of Ginkgo biloba L. Their structures were elucidated by various spectroscopic methods, and the structure of 1 was further confirmed by X-ray crystallographic analysis. The activities of the compounds were evaluated against platelet aggregation induced by platelet activating factor (PAF), and the preliminary structure-activity relationship was also discussed.

[Cerebrovascular and antiaggregative effects of GABA-docosahexaenoyldopamine conjugate].

The effects of GABA - docosahexaenoyldopamine (DHED) conjugate on the cerebral haemodynamics and thrombocyte aggregation were evaluated and compared to these of docosahexaenoyldopamine alone. The GABA - DHED conjugate was shown to significantly enhance the cerebral circulation in rats with a model of global transient cerebral ischemia, as compared to the intact animals. Administered alone, DHED increased the blood supply of both intact and ischemic brains to an equal extent. The GABA-DHED conjugate demonstrated the antiaggregative activity, but the effect was less expressed than that of DHED alone.

[Losartan for the correction of thrombocyte activity in patients suffering from arterial hypertension with metabolic syndrome].

The aim of the study was to evaluate therapeutic effects of losartan on intravascular thrombocyte activity (ITA) in patients suffering from arterial hypertension with metabolic syndrome (MS). The subjects of the study were 35 patients administered losartan 50 mg a day for 4 months. The dynamics of the following parameters were evaluated: anthropometric parameters, blood lipids, lipid peroxidation in blood plasma and thrombocytes, the anti-oxidative protection of the liquid part of blood and platelets, and ITA. Student criterion was used for statistical analysis. In patients with AH and MS losartan had a positive effect on peroxidation syndrome and optimized ITA. To maintain the positive effects, prolonged administration of losartan is needed. In order to lower body mass in AH patients with MS losartan should be used in combination with non-drug means.

[Sorption and contact-activating properties of the <> anastomosis zone: effect of suture material (communication II)].

The authors have carried out a comparative analysis of the interaction between two types of suture material with blood components, as well as studied the effect of heparin-mediated modification on the sorption and contact-activating processes in the zone of the anastomosis. The blood-compatible properties of the latter was assesses in vitro. It was determined that by minute 120 of the contact with blood, the largest amount of protein is had been absorbed by the anastomoses performed using the Prolene thread - 112 microg/cm2. Heparin-mediated modification made it possible to dramatically decrease the amount of the absorbed proteins. On the anastomoses performed with TiNi, additional treatment with heparin lead to an inconsiderable decrease in the protein amount. When identifying the absorbed proteins, we revealed dependence on the type of the suture material and modification with heparin. After a 60-minute contact with blood in the area of the anastomosis made with TiNi, absorbed were: albumin, immunoglobulins A, G, and transferrin. When using the Prolene thread, fibrinogen was noted to join. Additional heparinization exerted a favourable effect on the sorption processes in the area of the anastomosis wherein predominantly albumin and immunoglobulins A and G are predominantly absorbed. The parameters of the peak values and the rate of blood platelet aggregation were minimal in the area of the anastomoses done with TiNi with an additional treatment with heparin.

Synergism in the repression of COX-2- and TNFalpha-induction in platelet activating factor-stressed human neural cells.

Platelet activating factor (PAF; beta-acetyl-gamma-O-hexadecyl-l-alpha-phosphatidylcholine) triggers a rapid pro-inflammatory gene expression program in primary cultures of human neural (HN) cells. Two genes and gene products consistently induced after PAF treatment are the cytosoluble prostaglandin synthase cycloooxygenase-2 (COX-2) and the pro-apoptotic tumor necrosis factor alpha (TNFalpha). Both of these mediators are associated with the activation of inflammatory signaling, neural cell dysfunction, apoptosis and brain cell death, and both have been found to be up-regulated after brain injury in vivo. In this study we investigated the effects of the non-halogenated synthetic glucocorticoid budesonide epimer R (BUDeR), the novel PAF antagonist LAU-0901, and the electron spin trap and free radical scavenger phenyl butyl nitrone (PBN), upon early COX-2 and TNFalpha gene activation and prostaglandin E(2) (PGE(2)) release in PAF-stressed primary HN cells. The data indicate that these three biochemically unrelated classes of inflammatory repressors act synergistically in modulating PAF-induced up-regulation of COX-2, TNFalpha, and PGE(2) by quenching oxidative stress or inflammatory signaling, resulting in increased HN cell survival. These, or analogous classes of compounds, may be useful in the design of more effective combinatorial pharmacotherapeutic strategies in the treatment of complex neuro-inflammatory disorders.

[Comparative evaluation of the influence of sulfhydryl and phosphate ACE inhibitors on thrombocyte aggregation in patients suffering from atrerial hypertension with metabolic syndrome].

The purpose of the study was to compare the influence of two ACE inhibitors--captopril, a sulfhydryl one, and fozinopril, a phosphate one--on the aggregation activity of thrombocytes in patients suffering from arterial hypertension (AH) with metabolic syndrome (MS). Sixty-nine patients suffering from AH with MS were examined; 36 patients were administered captopril during 16 weeks, while 33 patients were treated with fozinopril during the same period of time. Changes in anthropometric parameters, blood lipid spectrum, lipid peroxidation in blood plasma and thrombocytes, and the antioxidative protection of liquid part of blood and platelets, as well as the aggregation activity of thrombocytes were assessed. The data received were processed using Student criterion and system multifactor analysis. The study shows that the use of fozinopril in patients with AH and metabolic syndrome attenuates peroxidation syndrome and optimizes thrombocyte aggregation. Prolonged fozinopril application will stabilize the achieved effect. Captopril did not have a positive effect on the parameters under study. In conclusion, fozinopril should be applied in combination with non-drug means to lower body weight in patients suffering from AH with MS.

The effects of Gingko biloba extract on acetic acid-induced colitis in rats.

BACKGROUND/AIMS: Gingko biloba is an antioxidant substance which has antagonistic activity on platelet-activating factor. We aimed to investigate the antioxidant effect and the histopathologic changes caused by Gingko biloba on acetic acid-induced colitis. METHODS: Totally 22 rats were divided into three groups. Group 1 (n=7) served as the control group. Group 2 (n=7) and Group 3 (n=8) were given 2 ml/day of 4% acetic acid by intracolonic instillation for three days. Gingko biloba (100 mg/kg) was then given only to Group 3 intraperitoneally for three days. Oxidative stress was assessed by determinate tissue and serum malondialdehyde (MDA) levels, and colonic damage was assessed by histologic examination. RESULTS: Depth of necrosis, extent of necrosis, degree of inflammation, extent of inflammation, fibrosis and total histologic scores in Group 2 were significantly higher than in the control group (p<0.05). The same parameters were lower in Group 3 versus Group 2, but the difference was not significant. Tissue and serum MDA levels in Group 2 were significantly higher than Group 1 (p<0.01 and 0.05, respectively). Again, the same parameters in Group 3 were lower than in Group 2, but the difference was not significant statistically. CONCLUSIONS: Gingko biloba did not significantly affect histopathological and oxidative stress parameters in experimental colitis.

[Biological action and clinical application of shark liver oil]. / Mechanizm dzialania i zastosowanie kliniczne oleju z watroby rekina.

Fish oils contain several active compounds that modify cell activity and influence various functions of the body. Shark liver oils are rich in alkylglycerols and squalene, but contain relatively low amounts of n-3 polyunsaturated fatty acids. Alkylglycerols may control immune response possibly throw modification of platelet activating factor (PAF) and diacylglycerol (DAG) production. Squalene enhances antigen presentation and induction of inflammatory response. Moreover, alkylglycerols and squalene have antitumour activity, that is possibly based on different mechanisms, ie., induction of apoptosis of neoplastic cells, suppression of signal transduction, inhibition of angiogenesis and promoting of transmembrane transport of cytotoxic agents. Shark liver oil has been found to be useful in treatment of conditions resulted from inadequate immune response, and in adjunctive treatment of several types of cancer.

Neuronal nuclear acetyltransferases involved in the synthesis of platelet-activating factor are located in the nuclear envelope and show differential losses in activity.

Neuronal nuclear fraction N1 was isolated from cerebral cortices of 15-day-old rabbits, and nuclear subfractions prepared, in order to study the location of nuclear lyso platelet-activating factor (lyso-PAF) acetyltransferase and alkylglycerophosphate (AGP) acetyltransferase, and factors that affect the loss of these two nuclear activities. Subfractionation of prelabelled N1 indicated that the nuclear envelope had the highest percentage of the radioactive acetylated products alkylacetylglycerophosphate (AAGP) and PAF, and the distribution of these phospholipids reflected phospholipid distributions in the nuclear subfractions. The majority (95%) of radioactive AAGP and PAF was also recovered in Triton X-100 extracts of prelabelled nuclei, suggesting that these acetylated lipids are located in nuclear membranes rather than in the nuclear matrix/chromatin. Of the nuclear subfractions, the envelope had the highest AGP and lyso-PAF acetyltransferase specific activities which were close to corresponding values seen in the parent N1 fraction. Thus the nuclear AGP and lyso-PAF acetyltransferases were principally localized to the nuclear membranes. Differentials in activity loss were seen for the two acetyltransferase activities. In the nuclear envelope fractions, the lyso-PAF acetyltransferase was the more susceptible to oxidation reactions which could be reversed or blocked by the use of reducing agents. In preincubations, N1 showed greater losses in lyso-PAF acetyltransferase activity than in AGP acetyltransferase activity, losses which were not attributable to oxidation. Addition of cytosolic fraction S3 to preincubations promoted losses for each acetyltransferase in N1, and gave evidence for cytosolic and endogenous nuclear contributions to the activity loss. Addition of okadaic acid to the preincubations did not prevent the decline of either acetyltransferase in intact nuclei, but did diminish the loss of nuclear lyso-PAF acetyltransferase activity promoted by S3 addition, and also blocked the loss of this acetyltransferase seen in preincubations of isolated nuclear envelopes. This suggests that nuclear lyso-PAF acetyltransferase is susceptible to okadaic acid-sensitive nuclear and cytosolic protein phosphatase activities, while AGP acetyltransferase may lose activity by the action of other phosphatases or by other mechanisms within the nucleus.

Postischemic renal oxidative stress induces inflammatory response through PAF and oxidized phospholipids. Prevention by antioxidant treatment.

Reperfusion injury is considered primarily an inflammatory response to oxidative stress. In vitro, oxygen free radicals induce the formation of oxidized phospholipids with platelet-activating factor (PAF) activity (PAF-like lipids). We examined the following: 1) whether PAF and PAF-like lipids are released during reperfusion; 2) the relationship between these phospholipids and oxidative damage on the one hand, and leukocyte recruitment in renal tissue on the other; and 3) whether antioxidant treatment influences the behavior of these phospholipids, the renal inflammatory response, and the outcome of postischemic acute renal failure. After 60 min of warm renal ischemia in rabbits, a release of PAF and, particularly, PAF-like lipids was seen in the first 15 min of reperfusion. In addition, the release of those phospholipids was associated with intense tissue DNA oxidation and with an increase in myeloperoxidase activity. Vitamin C was able to attenuate these postischemic oxidative changes, decrease PAF and PAF-like lipid levels, and, consequently, reduce myeloperoxidase activity. After 40 min of warm renal ischemia in rats, vitamin C treatment ameliorated renal function and structure. This is the first in vivo demonstration of the release of phospholipid oxidation products as part of an oxidative-inflammatory response after renal ischemia-reperfusion, with the release of phospholipid oxidation products significantly reduced by antioxidant treatment.

Attenuation of bleomycin-induced lung fibrosis in rats by mesna.

Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present study examined the effect of mesna on bleomycin-induced lung fibrosis in rats. Animals were divided into three groups: (1) saline control group; (2) Bleomycin group in which rats were injected with bleomycin (15 mg/kg, i.p.) three times a week for four weeks; (3) Bleomycin and mesna group, in which mesna was given to rats (180 mg/kg/day, i.p.) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the treatment. Bleomycin treatment resulted in a pronounced fall in the average body weight of animals. Bleomycin-induced pulmonary injury and lung fibrosis was indicated by increased lung hydroxyproline content, and elevated nitric oxide synthase, myeoloperoxidase, platelet activating factor, and tumor necrosis factor-alpha in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration and angiotensin converting enzyme activity in lung tissues. Moreover, bleomycin-induced severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and mesna reduced bleomycin-induced weight loss and attenuated lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, and concentrations of myeoloperoxidase, platelet activating factor, and tumor necrosis factor-alpha in lung tissues. Furthermore, mesna ameliorated bleomycin-induced reduction in reduced glutathione concentration and angiotensin activity in lung tissues. Finally, histological evidence supported the ability of mesna to attenuate bleomycin-induced lung fibrosis and consolidation. Thus, the findings of the present study provide evidence that mesna may serve as a novel target for potential therapeutic treatment of lung fibrosis.

Regulation of platelet-activating factor synthesis in human monocytes by dipalmitoyl phosphatidylcholine.

Platelet-activating factor (PAF) has a major role in inflammatory responses within the lung. This study investigates the effect of pulmonary surfactant on the synthesis of PAF in human monocytic cells. The pulmonary surfactant preparation Curosurf significantly inhibited lipopolysaccharide (LPS)-stimulated PAF biosynthesis (P<0.01) in a human monocytic cell line, Mono mac-6 (MM6), as determined by (3)H PAF scintillation-proximity assay. The inhibitory properties of surfactant were determined to be associated, at least in part, with the 1,2-dipalmitoyl phosphatidylcholine (DPPC) component of surfactant. DPPC alone also inhibited LPS-stimulated PAF biosynthesis in human peripheral blood monocytes. DPPC treatment did not affect LPS-stimulated phospholipase A(2) activity in MM6 cell lysates. However, DPPC significantly inhibited LPS-stimulated coenzyme A (CoA)-independent transacylase and acetyl CoA:lyso-PAF acetyltransferase activity. DPPC treatment of MM6 cells decreased plasma membrane fluidity as demonstrated by electron paramagnetic resonance spectroscopy coupled with spin labeling. Taken together, these findings indicate that pulmonary surfactant, particularly the DPPC component, can inhibit LPS-stimulated PAF production via perturbation of the cell membrane, which inhibits the activity of specific membrane-associated enzymes involved in PAF biosynthesis.

[The influence of nebivolol on thrombocyte aggregation in patients with arterial hypertension with metabolic sydrome].

The research was undertaken with the purpose to assess the efficiency of nebivolol for correction of thrombocyte aggregation capability in patients having arterial hypertension (AH) with metabolic syndrome (MS). 21 patients were administered nebivolol in a dose of 5 mg per day for a month. The dynamic changes in the following parameters were evaluated: anthropometric measurements, blood lipid spectrum, lipid peroxidation in serum and thrombocytes, antioxidative protectability of the liquid part of blood and platelets, thrombocyte aggregation activity. The results were processed using Student criterion and system multifactoral analysis. Nebivolol reduced peroxidation syndrome and optimized thrombocyte aggregation in patients with AH and MS. When administered for a long period of time, nebivolol is able to stabilize the achieved effect. Combining nebivolol application with use of non-drug means is necessary to reduce body weight in patients having AH with MS.

Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a sufficient level for triggering potentiation. Once the synaptic efficacy has changed, it becomes a long-lasting phenomenon only through a subsequent action of platelet-activating factor.

Influence of interleukin 1alpha on superoxide anion, platelet activating factor release and phospholipase A2 activity of naive and sensitized guinea-pig alveolar macrophages.

1. We studied the effect exerted by hr-interleukin-1alpha (IL-1alpha) on responsiveness of alveolar macrophages (AM) from naive and sensitized guinea-pigs, through O2.- production (by ferricytochrome C reduction), platelet-activating factor (PAF) release (by platelet aggregation), prostaglandin E2 (PGE2) release (by a radioimmunoassay), and cytosolic phospholipase A2 (cPLA2) activity (by hydrolysis of radioactive substrate). 2. In naive guinea-pig AM, 0.06 nM hr-IL-1alpha pretreatment decreased by 65% O2.- release stimulated with 10 nM fMLP. In contrast, O2.- production was not affected in sensitized guinea-pig AM. 3. O2.- release elicited by fMLP stimulation in both cell groups was affected by PLA2 inhibitors (10 microM bromophenacyl bromide, BPB or 10 microM methylprednisolone, MP). In contrast, 10 microM arachidonyl trifluoromethyl ketone (AACOCF3), a cPLA2 inhibitor, was ineffective. 4. In naive AM, PAF release was elicited by hr-IL-1alpha pretreatment and by separate fMLP-stimulation, but when the stimulus was added to hr-IL-1alpha-pretreated cells inhibition of PAF release was observed. In sensitized AM, PAF release was lower than that found in naive guinea-pig AM in both hr-IL-1alpha-pretreated and fMLP-stimulated cells. 5. PGE2 release was unaffected by hr-IL-1alpha pretreatment and it was decreased by fMLP in both naive and sensitized AMs. The latter released less PGE2 than naive cells in basal conditions and after fMLP treatment. 6. Sensitized AM showed a greater cPLA2 activity in all experimental conditions in comparison to naive cells. cPLA2 activity assayed in the cytosolic fraction was found to be enhanced by hr-IL-1alpha pretreatment and by fMLP stimulation in naive but not in sensitized AM. However, when the stimulus was added to hr-IL-1alpha-pretreated cells we observed a decrease in cPLA2 activity in the cytosol and an increase in the membranes, thus suggesting a translocation of enzymatic activity. 7. In conclusion, hr-IL-1alpha can modulate the responsiveness of AM from naive and sensitized guinea-pigs, as suggested by changes found in the release of PAF and O2.- and in cPLA2 activity; therefore, sensitization itself may affect cellular responsiveness.