Biomedical subjects

M Damon

Publications and source records attributed to M Damon.

At least 19 recordsLinked to original sources

PubMed2006

Number of intramuscular adipocytes and fatty acid binding protein-4 content are significant indicators of intramuscular fat level in crossbred Large White x Duroc pigs.

Intramuscular fat content is generally associated with improved sensory quality and better acceptability of fresh pork. However, conclusive evidence is still lacking for the biological mechanisms underlying i.m. fat content variability in pigs. The current study aimed to determine whether variations in i.m. fat content of longissimus muscle are related to i.m. adipocyte cellularity, lipid metabolism, or contractile properties of the whole muscle. To this end, crossbred (Large White x Duroc) pigs exhibiting either a high (2.82 +/- 0.38%, HF) or a low (1.15 +/- 0.14%, LF) lipid content in LM biopsies at 70 kg of BW were further studied at 107 +/- 7 kg of BW. Animals grew at the same rate, but HF pigs at slaughter presented fatter carcasses than LF pigs (P = 0.04). The differences in i.m. fat content between the 2 groups were mostly explained by variation in i.m. adipocyte number (+127% in HF compared with LF groups, P = 0.005). Less difference (+13% in HF compared with LF groups, P = 0.057) was noted in adipocyte diameter, and no significant variation was detected in whole-muscle lipogenic enzyme activities (acetyl-CoA carboxylase, P = 0.9; malic enzyme, P = 0.35; glucose-6-phosphate dehydrogenase, P = 0.75), mRNA levels of sterol-regulatory element binding protein-1 (P = 0.6), or diacylglycerol acyltransferase 1 (P = 0.6). Adipocyte fatty acid binding protein (FABP)-4 protein content in whole LM was 2-fold greater in HF pigs than in LF pigs (P = 0.05), and positive correlation coefficients were found between the FABP-4 protein level and adipocyte number (R2 = 0.47, P = 0.02) and lipid content (R2 = 0.58, P = 0.004). Conversely, there was no difference between groups relative to FABP-3 mRNA (P = 0.46) or protein (P = 0.56) levels, oxidative enzymatic activities (citrate synthase, P = 0.9; beta-hydroxyacyl-CoA dehydrogenase, P = 0.7), mitochondrial (P = 0.5) and peroxisomal (P = 0.12) oxidation rates of oleate, mRNA levels of genes involved in fatty acid oxidation (carnitine-palmitoyl-transferase 1, P = 0.98; peroxisome proliferator-activated receptor delta, P = 0.73) or energy expenditure (uncoupling protein 2, P = 0.92; uncoupling protein 3, P = 0.84), or myosin heavy-chain mRNA proportions (P > 0.49). The current study suggests that FABP-4 protein content may be a valuable marker of lipid accretion in LM and that i.m. fat content and myofiber type composition can be manipulated independently.

Adipocytes↗

PubMed2000

Stearoyl-CoA desaturase 1 coding sequences and antisense RNA affect lipid secretion in transfected chicken LMH hepatoma cells.

Hepatic stearoyl CoA desaturase (SCD) activity in chickens from a fat line is higher than that of chickens from a lean line and correlates with plasma triacylglycerol concentrations. Furthermore, in these lines, the hepatic SCD1 mRNA level is positively correlated with the adipose tissue weight. To analyze the contribution of the SCD1 gene in the regulation of adiposity in the early stages of triacylglycerol secretion, SCD1 coding sequence and antisense RNA expression vectors were transfected in LMH cells. After selection, these cells were analyzed with regard to SCD1 expression and lipid secretion. The amounts of secreted triacylglycerols and phospholipids were shown to be higher in LMH cells transfected with the SCD1 gene, but reduced in those transfected with the SCD1 antisense sequences when compared to cells transfected with the vector alone (without SCD1 sequences). These results provide direct evidence that the expression of the SCD1 gene plays a major role in the triacylglycerol and phospholipid secretion process.

Animals↗

PubMed2000

Characterisation of oxidative phosphorylation in skeletal muscle mitochondria subpopulations in pig: a study using top-down elasticity analysis.

In skeletal muscle, two mitochondrial populations are present which, on the basis of their localisation, are termed intermyofibrillar and subsarcolemmal mitochondria (IMF and SS, respectively). These two populations have different biochemical characteristics and show different responses to physiological stimuli. In this paper, we characterise the oxidative phosphorylation of SS and IMF using 'top-down' elasticity analysis. We excluded the possibility that their different characteristics can be attributed to a different degree of breakage of the two types of mitochondria due to the different isolation procedures used in their preparation. The higher respiration rate and higher respiratory control ratio shown by IMF compared with those shown by SS are principally due to the higher activities of the reactions involved in substrate oxidation as confirmed by the measurement of cytochrome oxidase activity. There is no difference in the leak of protons across the inner mitochondrial membrane between IMF and SS; a faster rate of ATP synthesis and turnover is driven by the lower membrane potential in SS compared with in IMF.

Adenosine Triphosphate↗

PubMed2000

First evidence of uncoupling protein-2 (UCP-2) and -3 (UCP-3) gene expression in piglet skeletal muscle and adipose tissue.

Uncoupling proteins (UCPs) facilitate proton transport inside the mitochondria and decrease the proton gradient, leading to heat production. Until now, the presence of UCP1 or other UCP homologs had not been detected in tissues of pig, a species where evidence for the presence of brown adipose tissue has only been provided in 2-3 month old animals. In the light of the improving knowledge on the UCPs family, we decided to examine both UCP2 and UCP3 mRNA expression in piglet skeletal muscle and adipose tissue. Using RT-PCR we have successfully cloned a partial UCP2 sequence and a complete UCP3 cDNA. UCP3's open reading frame (936bp) shares 90, 89 and 85% similarity with bovine, human and rat UCP3 nucleotide sequences, respectively. In 3-5 day old piglets, these genes are expressed in adipose tissue and in both longissimus thoracis (LT) and rhomboïdeus (RH) muscles, without any effect of muscle metabolic type. This is in good agreement with the measurement of the same membrane potential in mitochondria isolated from both types of muscles. In triiodothyronine-treated piglets, UCP3 mRNA is more expressed in LT than in RH muscle. These genes may be involved in the control of the energy metabolism of the piglet.

Adipose Tissue↗

PubMed2000

Phenobarbital induction of aldehyde dehydrogenase type 2 mRNA in mouse liver: a candidate region on chromosome 7 for a putative regulatory gene.

Phenobarbital (PB) strongly induces in the liver the expression of many genes encoding detoxication enzymes, such as the aldehyde dehydrogenase type 2 in the mouse (Aldh2). With the aim of identifying genes involved in this response, we have undertaken an approach based on a genetic analysis in mice. In a previous report, the genetic analysis of both the C57BL/6J (B6) x DBA/2J (D2) F1 and the (F1 x F1) F2 led us to the hypothesis that Aldh2 responsiveness to PB was under the control of one major locus independent of the structural gene. In the present study, the genetic analysis of the inducibility by PB of Aldh2 in the backcross population B6D2F1 x D2 has allowed us to confirm the involvement of a major regulatory gene in this mechanism. By searching for genetic linkage between this locus and a series of microsatellites DNA markers, we obtained indicative evidence for a region on chromosome 7, which may carry this gene.

Aldehyde Dehydrogenase↗

PubMed1999

Isolation of a cyp2b10-like cDNA and of a clone derived from a cyp2b10-like pseudogene.

By screening Balb/c male mouse liver cDNA library with a rat CYP2B1 cDNA probe, we have isolated a 1795 bp cyp2b10-like clone, referred to as P16. Its sequence exhibited 34 base differences (98% similarity) with the cyp2b10 published sequence, together with a 97% identity at the amino acid sequence level. By RT-PCR and PCR analyses with Balb/c female and male liver RNA and genomic DNA, using a region showing 8 base differences between the P16 and the cyp2b10 sequences, we have confirmed the identity of our cloned cDNA, and failed in finding a PCR product exhibiting a sequence 100% identical with that of cyp2b10. Our results therefore suggest that the P16 sequence is the authentic cyp2b10 sequence. We have also isolated a partial clone, P21, which 1609 bp sequence overlapped with that of P16, except for a T-->G transversion, giving rise to a premature TGA stop codon, indicating that it was derived from a pseudogene.

Amino Acid Sequence↗

PubMed1996

Isolation of a new mouse cDNA clone: hybrid form of cytochrome P450 2b10 and NADPH-cytochrome P450 oxidoreductase.

We have isolated a novel cDNA sequence from a male mouse liver library. It consists of an open reading frame containing no stop codon of 1348 bp which share 98% similarity with the cytochrome P450 2b10 followed by 95 nucleotides sharing 88% identity with the mouse NADPH cytochrome P450 oxidoreductase. Proteins are encoded by the opposite DNA strands. Genomic amplification excludes a library artefact or a de novo recombination event. RT-PCR analyses revealed expression of this clone in the liver of male and female mice as well as in kidney, lung and intestine. This cDNA was not, however, induced by phenobarbital. Preliminary results indicate that this cDNA could span more than 2.5 kb. This study is the first description of a cytochrome P450 cDNA sequence encoding part of both a cytochrome P450 and the NADPH cytochrome P450 oxidoreductase in mammalian liver.

Amino Acid Sequence↗

PubMed1996

Genetic analysis of the phenobarbital regulation of the cytochrome P-450 2b-9 and aldehyde dehydrogenase type 2 mRNAs in mouse liver.

The aim of this study was to investigate the effect of the genetic background on the phenobarbital inducibility of cytochrome P-450 2b-9, cytochrome P-450 2b-10 and aldehyde dehydrogenase type 2 mRNAs in mice. We analysed the basal expression and the phenobarbital inducibility of both cytochrome P-450 mRNAs by semi-quantitative specific reverse transcription-PCR analyses in five inbred mouse strains (A/J,BALB/cByJ,C57BL/6J, DBA/2J and SWR/J). Male mice constitutively expressed cytochrome P-450 2b-9 and cytochrome P-450 2b-10 mRNAs, but a number of differences in their response to phenobarbital were observed. In all these mouse strains, phenobarbital induced cytochrome P-450 2b-10 mRNA whereas it could have either a positive or a negative effect on cytochrome P-450 2b-9 expression, depending on the strain and the sex of the mice. Specifically, phenobarbital increased cytochrome P-450 2b-9 expression in C57BL/6J males while it decreased it in DBA/2J mice. Interestingly, dexamethasone was able to mimic the phenobarbital effect on both cytochromes P-450 in these two strains. Aldehyde dehydrogenase type 2 mRNA was always induced by phenobarbital, except in the C57BL/6J strain. Genetic analysis revealed that the phenobarbital-inducible phenotype was either a semi-dominant or a recessive trait in F1 animals from a C57BL/6J x DBA/2J cross for the cytochrome P-450 2b-9 and the aldehyde dehydrogenase type 2 genes, respectively. This study suggests that the genetic basis for phenobarbital induction in mice depends on the target gene, and that more than one regulatory step would by involved in this response pathway.

Aldehyde Dehydrogenase↗

PubMed1995

IFN-gamma activates superoxide anion production in blood monocytes from allergic asthmatic patients.

BACKGROUND: Peripheral blood monocytes may participate in allergic diseases by releasing inflammatory mediators. We have recently shown enhancement of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity in adherent human peripheral blood monocytes from allergic patients when immunoglobulin E (IgE) binds to its low affinity receptor. Interferon-gamma (IFN-gamma), a monocyte-activating lymphokine, has been shown to prime monocytes for superoxide anion release. OBJECTIVE: We hypothesized that IFN-gamma could directly activate blood monocyte superoxide anion release and evaluated its modulatory effect on IgE-induced superoxide anion release from those cells. METHODS: Seven patients with allergic asthma, 6 patients with allergic rhinitis, and five nonallergic controls were studied. We measured superoxide anion release from their blood monocytes using a chemiluminescence assay. Cells were either nonstimulated, or stimulated for 30 minutes with IFN-gamma and/or serum IgE. RESULTS: We found that IFN-gamma stimulated superoxide anion production and decreased the IgE-induced superoxide anion production after 30 minutes of IFN-gamma preincubation only in blood monocytes from patients with allergic asthma. CONCLUSIONS: These data suggest that IFN-gamma receptors may be increased and/or coupled to NADPH oxidase in allergic asthmatic patients.

Adult↗

PubMed1994

IgE produces monocyte superoxide anion release: correlation with CD23 expression. Comparison of patients with asthma, patients with rhinitis, and normal subjects.

Allergic inflammation involves many different cell types among which mononuclear cells, such as macrophages and monocytes, play an important role. These cells release numerous chemical mediators, including superoxide anion (O2.-). We evaluated the capacity of atopic serum to stimulate peripheral blood monocyte O2.- release. Thirteen untreated allergic patients (seven with asthma and six with rhinitis), and five nonallergic control subjects were studied. O2.- was measured in a photon-counting camera with Lucigenin-enhanced (Sigma Chemical Co., St. Louis, Mo.) chemiluminescence. Results were expressed (mean +/- SEM) in relation to basal values (peak/basal chemiluminescence values). Spontaneous production of O2.- was greater in allergic patients. Moreover, atopic serum stimulated O2.- production of blood monocytes in all subjects, but this was greater in subjects with allergic asthma than in subjects with allergic rhinitis and normal subjects. Anti-IgE immunoadsorption of atopic serum completely abrogated this effect, which was restored by the IgE-rich eluted fraction. IgE-induced O2.- release decreased as adherence duration increased and was correlated with surface CD23 expression. These results indicate that monocytes from allergic patients are in an activated state and that binding of IgE to their receptors generates O2.-, possibly by direct activation of blood monocyte reduced nicotinamide adenine dinucleotide phosphate oxidase.

Adult↗

PubMed1994

Enhancement of reactive oxygen species formation in stable and unstable asthmatic patients.

There is increasing evidence to suggest that human blood polymorphonuclear neutrophils (PMNs) and monocytes play an important role in the inflammatory processes of asthma. In asthmatic patients, PMNs and monocytes were shown to be activated more than in healthy subjects. We investigated the capacity of these two cell populations to generate reactive oxygen species (ROS) in stable and unstable asthmatic patients. The two populations of asthmatic patients were identified by asthma activity, as expressed by clinical events occurring within 2 weeks prior to the study. Oxygen species formation was analysed for isolated purified PMNs and monocytes (Mos) by chemiluminescence (CL) using lucigenin and luminol as luminescent probes. CL was determined on nonstimulated and on phorbol myristate acetate (PMA)-stimulated cells. The stimulatability coefficient (PMA-stimulated/nonstimulated cell ratio) of each cell population was then calculated. Resting PMNs and Mos generated significantly greater amounts of ROS in stable asthmatic patients, and much more in unstable asthmatic patients, as compared to healthy subjects, both in lucigenin and luminol enhanced CL. Non O2.- ROS production from PMA-stimulated PMNs and Mos was identical in unstable asthmatic patients and in healthy subjects, whereas a significant decrease was observed in stable asthmatic patients, as assessed by luminol enhanced CL. PMA-stimulated cells showed no difference in O2.- generation, as assessed by lucigenin enhanced CL. However, the stimulatability coefficient of all asthmatic patients was always significantly lower than that of healthy subjects. These results suggest that there are differences in priming and stimulation of Ros production from PMNs and Mos between stable and unstable asthmatic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridines↗

PubMed1993

Effects of flavonoids on the release of reactive oxygen species by stimulated human neutrophils. Multivariate analysis of structure-activity relationships (SAR).

In the present study we measured the inhibition by 34 compounds, either flavonoids or related substances, of the release of reactive oxygen species by human neutrophils after stimulation by three agents: the bacterial peptide N-fMetLeuPhe (FMLP), the protein kinase C activator phorbol myristate acetate (PMA) or opsonized zymosan (OZ), using two chemiluminescent probes, lucigenin or luminol in the presence or absence of horseradish peroxidase (HRP). The data matrix (34 x 7) was submitted to multivariate analysis: first, a correspondence factorial analysis to uncover levels of correlation among the biochemical parameters and the specificity of action of the test-compounds and second, a minimum spanning tree analysis that classified the chemical structures into a network describing both specificity and amplitude of the inhibition of the chemiluminescence response. The major conclusions of the analyses were: (a) opposition between inhibition of poly-morphonuclear leukocytes (PMNs) stimulated by FMLP and of PMNs stimulated by PMA or OZ implying that, for the molecules under study, there was a fundamental difference in the manner in which this inhibition occurred and, conversely, a difference in the nature of the stimulatory action of these activators. Molecules lacking hydroxyl groups on ring B, i.e. chrysin, chalcone, flavone and galangin, molecules glycosylated in position 7, i.e. hesperidin and naringin and ring B mono-hydroxylated molecules were, for the most part, at the origin of this dichotomy and might interfere with the membrane FMLP receptor; (b) a marked difference in chemiluminescence inhibition in the presence or absence of HRP that can be explained by the differential action of catechins compared to flavone and flavonol derivatives; (c) a similarity in biological profile between non-flavonoids such as chalcone and phloretin and low mean-activity flavonoids such as chrysin and galangin and between the non-flavonoid curcumin and the highly active flavonoid isorhamnetin; (d) a reaffirmation of the importance of ring A (C5,7) and ring B (C3',4') dihydroxylation, ring C (C3) hydroxylation, but also of the presence of a methoxy group on ring B in engendering high potency. This potency is generally decreased by C2-C3 saturation and by glycosylation. The most active molecules identified in this study provide valuable information for the selection of simpler molecules (e.g. metabolites accounting for the potency of orally administered flavonoids) for further structure-activity relationship (SAR) studies that could lead to the design of novel drugs or prodrugs.

Acridines↗

PubMed1993

Antioxidant activity of micronized diosmin on oxygen species from stimulated human neutrophils.

Flavonoids are known to reduce reactive oxygen species released by polymorphonuclear neutrophils (PMNs) in vitro. We have studied the effects of S5682 (Daflon 500 mg), a purified flavonoid fraction composed of 90% diosmin and 10% hesperidin. S5682 produced a dose-dependent inhibition of the luminol chemiluminescence (CL) induced by phorbol myristate acetate on PMNs (IC50 = 5 x 10(-5) M), with no effect on superoxide anion (O2.-) formation and on cellular superoxide dismutase activity as determined by lucigenin-amplified CL. The CL results were confirmed by the hydrogen peroxide (H2O2) determination showing that S5682 reduced H2O2 formed through either PMN stimulation (IC50 = 1.6 x 10(-6) M) or an in vitro enzymatic mechanism (IC50 = 2 x 10(-6) M). S5682 inhibited luminol-dependent CL induced by H2O2 (IC50 = 5 x 10(-6) M). However, O2 was not formed from H2O2 in contact with S5682 and the UV spectrum of this compound was not modified. In contrast, S5682 inhibited luminol-dependent CL induced by H2O2 in the presence of horseradish peroxidase (IC50 = 3 x 10(-6) M), and the UV spectrum of S5682 was modified. Luminol-dependent CL induced by hypochlorite (OCl- 10(-5) M) was also inhibited by S5682 (IC50 = 7 x 10(-5) M). This inhibitory effect was similar to that of sodium azide on myeloperoxidase activity. Moreover, OCl- 5 x 10(-4) M also altered the UV spectrum of S5682 10(-4) M. These results indicate that S5682 could be active on the H2O2-OCl(-)-myeloperoxidase system.

Acridines↗

PubMed1993

Effect of nedocromil sodium on sulfidopeptide leukotrienes-stimulated human alveolar macrophages in asthma.

Alveolar macrophages (AM) may take part in the amplification of the inflammatory mechanism involved in asthma. During an asthma attack, mast cells and eosinophils release arachidonic acid derivative mediators of inflammation such as sulfidopeptide leukotrienes. Among them, LTC4 has been shown to be present in bronchoalveolar fluid. In asthmatic patients, we showed that the ability of AM to transform LTC4 into its derivatives LTD4 and LTE4 was related to the intensity of the local inflammation observed during endoscopy. AM from asthmatics incubated in the presence of LTC4 or LTE4, generated LTB4 and 5-HETE, which are potent chemoattractants. Nedocromil sodium (10(-4) M) decreased LTB4 releasability and intracellular 5-HETE concentrations in zymosan-stimulated AM from asthmatic patients, and was shown to decrease the LTC4 or LTE4-promoted formation of LTB4 and 5-HETE.

Adolescent↗

PubMed1992

Enhanced esterification process of 5-hydroxyeicosatetraenoic acid (5-HETE) in PMN from asthmatic patients.

Polymorphonuclear neutrophils (PMN) generate 5-HETE which can be retained within cells as free metabolites or esterified into cellular lipids. Since this metabolite has been shown to have certain inflammatory properties, we compared the generation and distribution profile of 5-HETE in A 23187-stimulated PMN from asthmatic patients (AP) and normal subjects (NS). 5-HETE was analyzed using RP-HPLC. After 5 min, total 5 HETE generation was similar in the two populations. However, esterified 5-HETE was significantly enhanced in AP (72 +/- 3% versus 47 +/- 2% of the total synthesis, p less than 0.005), whereas intracellular free 5-HETE was decreased (13 +/- 3% versus 37 +/- 4%, p less than 0.005) and similar low release was observed. Kinetic studies showed that PMN from AP esterified 5-HETE more rapidly and to a greater extent than PMN from NS. By contrast, more intracellular free 5-HETE was recovered in PMN from NS. Esterification seems to be the major pathway of 5-HETE metabolism in PMN from AP. Moreover, we showed that most of the 5-HETE added exogenously was esterified into cellular lipids. In these experimental conditions, PAF-induced migration of PMN was increased. The enhanced ability of PMN to migrate could be due to the increase of 5-HETE esterification process.

Adult↗

PubMed1992

Platelet-activating factor production during hemodialysis: effect of BN 52021.

Platelet activating factor (PAF) production and platelet-lipoxygenase activity were studied during hemodialysis (HD) with cuprophane membranes. Six patients were treated with first-use dialyzers (FU), and 6 patients with reused dialyzers (RU). In a random and double-blind design, 2 HD were performed for each patient, with or without BN 52021 pretreatment, a selective PAF antagonist. Platelet and leukocyte counts were performed before pretreatment and 30 min before HD starting (T-30), at the beginning of HD (T0) and after 15 and 30 min of HD (T15, T30). PAF production was analyzed by direct phase HPLC. To determine platelet-lipoxygenase activity, 12-HETE was detected by reverse phase high performance liquid chromatography (HPLC) after blood stimulation by the ionophore A23187. In the FU group, PAF and 12-HETE were produced during the first 30 min of HD. After BN 52021 pretreatment, PAF production was suppressed and platelet-lipoxygenase activity reduced. In the RU group, neither PAF nor 12-HETE production occurred, and BN 52021 had no effect. We conclude that PAF, which was involved in both platelet and leukocyte activation that occurred during hemodialysis, can be considered as a bio-incompatibility marker.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1992

Arachidonate 5-lipoxygenase metabolism in human neutrophils from patients with asthma: in vitro effect of nedocromil sodium.

Among the cells which participate in amplification of the local inflammatory reaction in asthma, neutrophils (PMN) are pro-inflammatory cells that can generate inflammatory mediators and arachidonic acid derivatives in particular. In asthmatic patients (AP) with attacks, the capacity of blood PMN to produce 5-lipoxygenase metabolites was investigated and compared to the response in healthy subjects (HS). PMN from 6 AP and from 6 HS were stimulated by calcium ionophore A23187 and arachidonate 5-lipoxygenase metabolites were analyzed by reverse-phase HPLC. LTB4, 6-trans LTB4, omega OH-LTB4 and 5-HETE were identified. In AP, total LTB4 synthesis was enhanced as compared to synthesis with PMN in HS. But the total 5-HETE synthesis by PMN from AP was decreased. Thus, the inflammatory potential of PMN from AP was enhanced in comparison to HS. The anti-inflammatory effect of nedocromil sodium (NS) was studied in the 5-lipoxygenase metabolism of arachidonic acid. NS (10(-4) mol/l) inhibited total LTB4 synthesized by PMN in AP but not in HS. We conclude that NS affects leukotriene synthesis only in cells with enhanced inflammatory potential.

Adult↗

PubMed1992

Increased oxygen species generation in blood monocytes of asthmatic patients.

Besides eosinophils, inflammatory processes in asthma are characterized by an infiltration of inflammatory cells, including mononuclear phagocytes, such as alveolar macrophages (AM) and blood monocytes, in the airways. Monocyte activation has been observed in the blood after exercise or allergen-induced asthma. Stimulated AM in chronic and stable asthmatic patients have been shown to release oxygen species. We thus investigated the intensity of the activation of monocytes from 18 asthmatic patients compared with 18 healthy subjects. Oxygen species release was analyzed for monocytes in suspension by chemiluminescence using a luminometer and for monocytes maintained in adherence using conventional assay and video imaging camera. Circulating blood monocytes in suspension from asthmatic patients and control subjects showed the same baseline free radical release. Monocytes in suspension from asthmatic patients were more stimulatable by PMA: specifically, monocytes release more H2O and peaks of O2-. are sooner; moreover, peaks of total free radical release are higher, and this plateau is sustained. Compared with monocytes from control subjects, those from asthmatic patients evaluated after adherence show a higher baseline for O2-. and higher total free radical release. Monocytes from asthmatic patients spontaneously release more O2-. over time in nonstimulated cells and release more O2-. with PMA stimulation; they show the same peak level total free radical release as those from control subjects after stimulation. SOD activity analysis on adherent monocytes was lower in asthmatic compared with control subjects. These data show that monocytes from asthmatic patients were activated compared with control monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridines↗