Biomedical subjects

M Lagarde

Publications and source records attributed to M Lagarde.

At least 127 records · Page 7Linked to original sources

PubMed1994

Oestradiol-induced changes in the composition of phospholipid classes of quail oviduct: specific replacement of arachidonic acid by docosahexaenoic acid in alkenylacyl-glycerophosphoethanolamine.

The phospholipid composition and the molecular species of the major subclasses of ethanolamine and choline glycerophospholipids were determined during the natural or oestradiol-induced development of the quail oviduct. The phospholipid concentration increased significantly during oviduct development, and the proportion of ethanolamine glycerophospholipids (EPL) remained constant while that of choline glycerophospholipids increased. The immature oviduct contained the majority of its endogenous arachidonic acid mass (71%) in EPL, mainly in alkenylacyl-glycerophosphoethanolamine (alkenylacyl-GPE) (49% of the total). Oestrogen treatment induced the depletion of 20:4,n-6 specifically from this pool, which indicates the biological importance of 20:4,n-6 molecular species in alkenylacyl-GPE as substrates for the oviduct phospholipases activated by oestradiol, and suggests that this EPL subclass is involved in the oestrogen-induced cell proliferation. Another striking result was the marked increase in 22:6,n-3 EPL molecular species following the oestradiol treatment and more particularly the strict substitution of 20:4,n-6 by 22:6,n-3 in alkenylacyl-GPE. We speculate that alkenylacyl-GPE molecular species containing 22:6,n-3 may participate in the arrest of oestrogen-induced proliferation.

Animals↗

PubMed1994

Decreased arachidonic acid metabolism in human platelets by autologous neutrophils: possible role of cell adhesion.

The amount of the 12-lipoxygenase and cyclo-oxygenase products, 12(S)-hydroxy-(Z,Z,E,Z)-5,8,10,14-eicosatetraenoic acid (12-HETE) and 12(S)-hydroxy-(E,E,Z)-5,8,10-heptadecatrienoic acid (HHT), in human platelets stimulated by thrombin (0.1 and 2.5 units/ml), was studied in the presence of autologous neutrophils. A decreased formation of both products was induced by unstimulated neutrophils or neutrophils challenged with N-formylmethionyl- leucyl-phenylalanine (0.1 microM) or Ca2+ ionophore A23187 (0.15 microM). The effect of neutrophils was observed only in the presence of Ca2+. 12-HETE and HHT were also produced in platelets stimulated with thrombin in the absence of Ca2+ and/or Mg2+, but their level was not altered by neutrophils. 12(S),20-Dihydroxy-(Z,Z,E,Z)-5,8,10,14-eicosatetraenoic acid (12,20-DHETE), the cytochrome P-450 product from 12-HETE in neutrophils, was hardly detected, and its level did not compensate for the decrease in 12-HETE observed after platelet and neutrophil co-incubation. 5(S),12(S)-Dihydroxy-(E,Z,E,Z)- 6,8,10,14-eicosatetraenoic acid (5(S),12(S)-DHETE), the 5-lipoxygenase product of 12-HETE in neutrophils, was never detectable. In addition, the inhibition of 12-HETE and HHT formations appeared not to be due to degradation or thrombin uptake by neutrophils, nor was the decrease observed when the two cell populations were physically separated. A monoclonal antibody against the human platelet glycoprotein GMP140 (CD62), mediating Ca(2+)-dependent platelet-neutrophil adhesion, mimicked the inhibitory effect of neutrophils in a dose-dependent fashion. Furthermore, the 12-HETE and HHT productions were not affected when platelets were stimulated in the presence of neutrophils previously incubated with sialidase, which removes the sialic acid from a sialyl Lewis(x) structure assumed to be the neutrophil receptor for platelet GMP140. We conclude that the decrease in thrombin-stimulated 12-HETE and HHT formation observed when platelets were co-incubated with autologous neutrophils might be the consequence of platelet-neutrophil adherence, presumably through platelet GMP140.

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

PubMed1994

Purification and characterization of glutathione peroxidase from human blood platelets. Age-related changes in the enzyme.

Platelet glutathione peroxidase (GPx) is known to play a pivotal role in controlling the level of lipid hydroperoxides, especially those resulting from the 12-lipoxygenase activity. GPx was purified from the cell cytosol by more than 700-fold using an exchange chromatography, FPLP, gel filtration and covalent fixation. Isoelectric focusing revealed a peak activity at pH 5.1. The molecular mass of the enzyme was found between 90 and 100 kDa by gel filtration, and was approximating at 23 kDa by SDS-PAGE. A polyclonal antibody raised against commercial bovine erythrocyte GPx recognized the human platelet enzyme. It is concluded that human platelet GPx is likely a homotetramer of 92 kDa as described for most other sources. We have also found that the decreased platelet GPx activity observed in platelets from elderly people is associated with a lower content of the immunoreactive enzyme.

Adult↗

PubMed1994

Incorporation of arachidonic and docosahexaenoic acids into phospholipids of rat brain membranes.

The incorporation of [3H]arachidonic acid (20:4n-6) into rat brain membranes and its mobilization in response to norepinephrine, a relevant neuromediator were studied. The most efficient [3H]20:4n-6 incorporation was in inositol glycerophospholipids (PI) where it reached a plateau after 10 min incubation, while this incorporation was very weak in choline glycerophospholipids (PC). In contrast, the esterification of docosahexaenoic acid, another polyunsaturated fatty acid occurring at high level in brain, was similar in PI and PC, the incorporation in PI being 8-fold lower than that of 20:4n-6. The newly esterified [3H]20:4n-6 was exclusively found in the 1,2-diacyl subclasses of PI and PC. The bulk of incorporation was in the 18:0/20:4n-6 molecular species of 1,2-diacyl-glycerophosphoinositol and in 16:0/20:4n-6 + 18:1/20:4n-6 molecular species of 1,2-diacyl-glycerophosphocholine, which agrees with the usual location of 20:4n-6 in brain phospholipid classes. Upon norepinephrine treatment, [3H]20:4n-6 was not released from PC, but was dose-dependently decreased in PI, the release being significant from 10(-5) M of the agonist. These results suggest that 20:4n-6 exhibits a high specific turnover in brain PI and is mobilized from this class upon relevant neuromediator stimulation. The acellular system used preserved the specificity of enzymes catalyzing the polyunsaturated fatty acid incorporation and release and could be helpful for studying their turn over in brain.

Animals↗

PubMed1994

Increased glutathione peroxidase activity in human blood mononuclear cells upon in vitro incubation with n-3 fatty acids.

Fish oil-enriched diets have been shown to increase the n-3 polyunsaturated fatty acid (PUFA) content of cell membranes, in vivo, and to simultaneously enhance the glutathione peroxidase (glutathione: H2O2 oxidoreductase, EC 1.11.1.9) (GSH-Px) activity of platelets and erythrocytes both in animals and humans. The present study aimed to determine whether in vitro enrichment of human peripheral blood mononuclear cells (PBMC) with either eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) might have similar influence on the GSH-Px activity of these cells. Pretreatment of human PBMC for a short period of time (90 min) with 5 microM of either EPA or DHA was sufficient to induce a significant enrichment of cellular phospholipids in the corresponding fatty acid. This was accompanied by an increased GSH-Px activity of these cells. This stimulatory effect proved to be specific of n-3 fatty acids since it was not observed with saturated, monounsaturated or n-6 polyunsaturated fatty acids. Neither EPA nor DHA had a direct influence on the GSH-Px activity of PBMC in cell-free preparations. Both fatty acids had no influence on the distribution of total proteins between the cytosolic and the particulate compartments. EPA did not significantly alter the GSH-Px kinetic behavior thus suggesting an increased expression of the enzyme. In addition, DHA slightly but significantly decreased the proliferative response of PBMC to the mitogenic stimulation by Con A whereas EPA only tended to do so.

Cell Division↗

PubMed1994

Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats.

The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1, 3, 6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was significantly lower in SHR than in WKY rats, except at the age of one month. The decrease of this enzyme activity could induce an increased cellular generation of radical species and lipid peroxidation, which might be link to hypertension.

Aging↗

PubMed1994

Phosphodiesterase inhibitory profile of some related xanthine derivatives pharmacologically active on the peripheral microcirculation.

The cyclic nucleotide phosphodiesterase (PDE) inhibitory profile of four related xanthine derivatives: pentoxifylline (BL 191), propentofylline (HWA 285), torbafylline (HWA 448) and albifylline (HWA 138), pharmacologically active on the peripheral and/or cerebral microcirculation was established using the four main PDE isoforms present in rat heart cytosol. HPLC on a Mono Q ion-exchange column resolved four separate cyclic nucleotide PDE activities: a calmodulin-activated fraction (PDE I), a cGMP-stimulated fraction (PDE II), a cAMP-specific rolipram-sensitive fraction (PDE IV) and a cGMP-inhibited fraction (PDE III). Among the four compounds studies, only torbafylline and pentoxifylline inhibited more efficiently the calcium plus calmodulin-stimulated than the basal activity of PDE I. The four xanthine derivatives inhibited more potently the cGMP-stimulated than the basal activity of the cGMP-stimulatable PDE II, propentofylline being the most inhibitory (IC50: 20 microM). Except for propentofylline, which exhibited a marked selectivity toward the rolipram-sensitive PDE versus the cGMP-inhibited PDE III, the other xanthines modestly (IC50 in the 10(-4) M range) inhibited both cAMP-specific isoforms with similar potency. Propentofylline proved to be the best inhibitor whatever the considered isoform whereas torbafylline exhibited the weakest inhibitory potency with, however, some selectivity for PDE I.

Animals↗

PubMed1994

Phospholipase A2 inhibitors regulate the proliferation of normal uterine cells.

The effects of inhibitors of phospholipase A2, cyclooxygenase, lipoxygenase and cytochrome P450 activity on the proliferation of normal rat uterine stromal cells (UIII) were studied. At non-cytotoxic doses, inhibitors of cyclooxygenase, lipoxygenase and cytochrome P450 activity had no effect; UIII cells did not lose their ability to synthesize and secrete arachidonic acid metabolites, mainly prostaglandin I2 and prostaglandin E2, after successive passages. Inhibition of prostaglandin production did not affect their proliferation. In contrast, phospholipase A2 inhibitors significantly reduced UIII cell proliferation in a reversible and dose-dependent manner. Aristolochic acid was the most potent inhibitor with an IC50 of 0.3 mumol/l on day 7 of culture. Moreover, low doses of arachidonic acid stimulated UIII cell proliferation. Thus the proliferation of normal uterine stromal cells appears to be independent of arachidonic acid oxygenated metabolites, contrary to what is observed in tumor cells, but requires an intact phospholipase A2 pathway.

Animals↗

PubMed1994

Stable isotope tracer and gas-chromatography combustion isotope ratio mass spectrometry to study the in vivo compartmental metabolism of docosahexaenoic acid.

A gas-chromatography combustion isotope ratio mass spectrometry (GCC-IRMS) method using carbon 13 (13C)-stable isotope to trace n-3 polyunsaturated fatty acids (PUFA) turnover in vivo is presented. Natural 13C abundance of commercial n-3 PUFA was measured from 100 to 300 ng of fatty acids and was -27.58, -27.83, and -28.16 for 22:6n-3, 22:5n-3, and 20:5n-3, expressed as delta 13C /1000 versus Pee Dee Belemnite (PDB), respectively. Precision of delta 13C /1000 values was comparable for the three PUFA and gave relative standard deviations of 0.95-0.97%. Isotope enrichment of 0.0010 at.% could be detected. Triglycerides enriched in [13C]22:6n-3 ([13C]22:6-TG) were synthesized by growing a microalgae on [1-13C]glucose. [13C]22:6n-3 represented 36 wt.% of total triglyceride fatty acids and had an isotope enrichment of 2.0420 at.%, which was the double of natural abundance. The isotope enrichment of 22:6n-3 in lipids from rat lipoproteins and red cells could be followed as a function of time after ingestion of 3 mg [13C]22:6-TG and showed specific patterns according to the lipid compartments. The retroconversion of [13C]22:6n-3 was also detected in HDL phosphatidylcholine by the appearance of [13C]22:5n-3 and [13C]20:5n-3. On the other hand, 22:6n-3 natural 13C abundance in human lipid classes of lipoproteins and blood cells has been measured using 10 ml plasma, even for the more limiting lipid compartments in terms of 22:6n-3 dose size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Prostaglandin E2 production by uterine stromal cell line UIII: regulation by estradiol and evidence of an ethanol action.

We have recently established a uterine stromal cell line (UIII). The purpose of the present study was to determine whether these cells have retained the ability to produce and release prostaglandins after several passages and whether this production was regulated. UIII cells, grown in basal conditions, released a very low amount (40.6 +/- 2.9 pg/24h/10(6) cells) of prostaglandin E2 (PGE2) though cellular content was more elevated (192 +/- 23 pg/10(6) cells). Ethanol increased the cellular content but decreased the release of PGE2, whereas estradiol 17 beta (E2) increased it in a dose-dependent manner, but had no effect on the cellular content. The PGE2 release by cells grown in medium containing 10 microM arachidonate (AA) reached 1.39 +/- 0.05 ng/24h/10(6) cells, and was further increased to 2.1 +/- 0.1 ng/24 h/10(6) cells by the addition of ethanol. Under the latter condition, E2 was ineffective. This study also showed that UIII cells expressed an immunoreactive pancreatic type 14 kD PLA2. A substantial increased 14 kD PLA2 expression was observed in ethanol-treated cells, suggesting that ethanol-effect on prostaglandin production might be partly mediated by PLA2 increase. Medium supplementation with arachidonate also resulted in a significant increase of intracellular 14 kD PLA2 expression. The present results showed that uterine stromal UIII cells have retained the enzymatic machinery to produce PGE2. Moreover these data demonstrate that ethanol and E2 affect differently uterine PGE2 production.

Animals↗

PubMed1994

Formation, metabolism, and action of hepoxilin A3 in the rat pineal gland.

The present study was undertaken to investigate the possible formation of hepoxilin A3 in the rat pineal gland and to study the potential physiological role for this compound in this tissue. Incubation of homogenates of rat pineal glands with arachidonic acid (66 microM) led to the appearance of hepoxilin A3 (HxA3) analyzed as its stable trihydroxy derivative, trioxilin A3 by gas chromatography in both the electron impact and negative ion chemical ionization modes. Endogenous formation of HxA3 is estimated to be 1.43 +/- 0.66 ng/micrograms of protein. This amount is not modified when the tissue is boiled (2.07 +/- 0.66 ng/micrograms of protein). However, the formation of this compound was stimulated to 21.26 +/- 5.82 ng/micrograms of protein when exogenous arachidonic acid was added to the homogenate. Addition of the dual cyclooxygenase/lipoxygenase inhibitor BW 755C (10 micrograms) resulted in a partial blockade of hepoxilin formation. Using [1-14C]HxA3, we demonstrated that the pineal gland contained hepoxilin epoxide hydrolase, which hydrolyzed HxA3 into trioxilin A3. This hydrolysis was inhibited by 1 mumol/L of 3,3,3-trichloropropene-1,2-oxide. In a separate study, HxA3 in the presence of 3,3,3-trichloropropene-1,2-oxide to block the hydrolysis of HxA3 decreased the production of cyclic AMP in cultured organ rat pineals after stimulation with 5'-N-ethylcarboxamidoadenosine, an A1/A2 adenosine receptor agonist. This effect is stereospecific because the (8S)-enantiomer is more active in decreasing cyclic AMP production (-88.7%) than the (8R)-enantiomer. This is the first demonstration of the presence, metabolism, and action of HxA3 in the rat pineal gland.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1994

Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain.

The uptake and metabolism of [3H]docosahexaenoic acid (DHA) esterified at the sn-2 position of lysophosphatidylcholine (lysoPC DHA) and in the unesterified form, both bound to albumin, was studied in 20-day-old rats. LysoPC DHA was preferentially recovered in the brain (4-5% of the injected radioactivity) over the unesterified form of DHA (0.3-0.4%). Conversely, the lysoPC form was taken up less than or at the same extent as the unesterified form by the liver, heart, and kidney. In the brain, DHA was mainly recovered in phosphatidylethanolamine whether the esterified or the unesterified form was used, although DHA from lysoPC was esterified at the same extent in phosphatidylcholine and phosphatidylethanolamine after 2.5 min. The uptake of labeled palmitic, oleic, linoleic, and arachidonic acids, esterified or not in lysophosphatidylcholine, was also studied in brain, liver, heart, and kidney. Only the brain preferentially incorporated unsaturated (but not saturated) lysoPC, with the uptake increasing with the degree of unsaturation of the fatty acid moiety. These results strongly suggest that the young rat brain specifically utilizes albumin-lysoPC-containing polyunsaturated fatty acids.

Animals↗

PubMed1994

Regulation of quail oviduct phospholipase A2 activity by estradiol.

The phospholipase A2 (PLA2) activity was measured in the oviduct of immature and estradiol benzoate (EB)-treated quails. The pH profiles demonstrate the presence of two PLA2 isoforms in the avian oviduct: a neutral isoform, optimally active at pH 7-7.5 and calcium independent, responsible for most of the hydrolytic activity in the immature oviduct and poorly stimulated by estradiol; and an alkaline isoform, optimally active at pH 8-9.5 and calcium dependent, with little activity in the immature tissue but markedly stimulated by EB. After EB injection, PLA2 activation occurs at first during the prereplicative period of oviduct cells (+172% at 6 h), it is dose dependent from 0.01 to 1 mg/kg EB and can be prevented by cycloheximide together with ornithine decarboxylase activation. Moreover, estradiol was inactive on cell-free extracts of immature oviducts. These results suggest that EB increases PLA2 activity through gene activation and de novo protein synthesis. The correlation between the early stimulation of PLA2 activity and the proliferation of oviduct cells is discussed.

Animals↗

PubMed1994

Antibiotics and production of granulocyte-macrophage colony-stimulating factor by human bronchial epithelial cells in vitro. A comparison of cefodizime and ceftriaxone.

Cultured human bronchial epithelial cells (HBEC) produce both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 8 (IL-8). The influence of cefodizime (CAS 69739-16-8), a new broad spectrum cephalosporin with immunostimulatory effects, and ceftriaxone on the production of GM-CSF and IL-8 in HBEC primary cultures was investigated. HBEC were isolated from biopsy specimens obtained during fibreoptic bronchoscopy in 12 patients (most frequent diagnosis: chronic bronchitis). Confluent monolayers of HBEC cultured on collagen were incubated for 24 h in a medium without study drugs (spontaneous production) or containing cefodizime or ceftriaxone at the clinically relevant concentrations of 1, 10 and 100 mg/l, with or without tumor necrosis factor alpha (TNF alpha, 100 U/ml). GM-CSF and IL-8 were measured in supernatant by ELISA technique. TNF alpha alone led to a significant (p < 0.005) increase in both GM-CSF and IL-8 production. Cefodizime induced a significant (p < 0.05), dose-dependent increase in GM-CSF release. No additive effect of cefodizime with TNF alpha was observed. Cefodizime did not affect IL-8 production and ceftriaxone had no influence on cytokine production. This is the first report of a stimulatory effect of a beta-lactam antibiotic on cytokine production by epithelial cells. GM-CSF production by epithelial cells is an important immunological step for neutrophil and monocyte recruitment and cell priming during lung defence. Previous studies with cefodizime in immunodepressed subjects have shown activation of phagocytosis and phagocytosis-related functions in non-lung phagocytes. An indirect mechanism of action, similar to that indicated by our results, may have been responsible for these stimulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

S-adenosyl-l-methionine inhibits phosphoinositide metabolism in the rat brain synaptosomal suspensions.

S-adenosyl-l-methionine (AdoMet) has been reported to affect events linked to noradrenergic neurotransmission. In the present work, we studied the effect of AdoMet on norepinephrine (NE)-stimulated inositol phosphate production in 3H-inositol-labelled crude synaptosomal suspensions of rat brain. AdoMet (50-1000 microM) decreased both the synthesis of labelled polyphosphoinositide (30-50%) and the release of inositol mono- and bisphosphate (40-50%). The AdoMet effect was not dependent on NE concentration (10-1000 microM), suggesting that the inhibition of inositol phosphate release was not the result of a modification of the norepinephrine binding to its receptor sites. S-adenosyl-L-homocysteine (AdoHcy) (1 mM) an inhibitor of methyltransferase activities, partially inhibited (70%) the AdoMet (0.1 mM) effect, indicating that the methylation processes cannot explain all the effects observed. We conclude that, in addition to previously reported effects of AdoMet on NE transport, AdoMet may reduce NE-linked intracellular signalling.

Analysis of Variance↗

PubMed1993

Phosphatidic acid stimulates the rolipram-sensitive cyclic nucleotide phosphodiesterase from rat thymocytes.

The role of phospholipid metabolites in the modulation of cyclic AMP degradation during the early response of rat thymic lymphocytes to mitogenic stimulation was investigated by measuring their in vitro effect on the activity of five different cyclic nucleotide phosphodiesterase forms separated from thymocyte cytosol by means of an HPLC technique. Arachidonic acid was found to markedly inhibit four of the enzyme forms, with IC50 ranging from 14 to 60 microM, while its hydroperoxy and hydroxy derivatives proved inefficient. Dioctanoylglycerol, a biologically active diacylglycerol, was weakly inhibitory while phosphatidic acid, the diacylglycerol phosphorylated derivative, markedly stimulated the two cyclic-AMP-specific type-IV forms identified in thymocyte cytosol, by 50 and 70%. In intact cells labelled with tritiated arachidonate, the mitogenic lectin concanavalin A induced a rapid 4-5-fold increase in radiolabelled phosphatidic acid which peaked at 1 min, and remained elevated for at least 30 min. These observations suggest that phosphatidic acid formed during the mitogenic stimulation of T-cells might be responsible for an early activation of cyclic AMP degradation with, as a consequence, a lowering of cyclic AMP level, which is reported to be necessary for the occurrence of the first steps of mitogenesis.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1993

Variations in the fatty acid composition of lipid classes from lipoproteins in elderly women.

Fatty acid composition of lipid classes and NMR spectra of lipoproteins were compared in 6 young (24-35-year-old) and 6 elderly (79-90-year-old) women. Cholesteryl ester, triglyceride and protein content of LDL in elderly women were significantly higher (+52-57% and +20% for lipids and proteins, respectively) than those observed in young women. HDL lipid levels were similar in the two groups. The proportion of linoleic acid (mainly in cholesteryl esters and phospholipids) of each lipoprotein species was always lower in octogenarians when compared with young females (lowering of 13-28% and 27-46% for cholesteryl esters and phospholipids, respectively). Conversely, the proportions of mono-unsaturated fatty acids (mainly oleic acid) increased in all lipid classes, although this was only significant in cholesteryl esters from each lipoprotein species. NMR spectra of lipoproteins showed a restricted mobility of acyl chain terminal CH3 groups in old women which was significant only in VLDL and HDL3. This suggests that the decrease of linoleic acid could affect the lipid mobility in lipoproteins of elderly women.

Adult↗

PubMed1993

The impaired in vitro production of interleukin-2 in HIV infection is negatively correlated to the number of circulating CD4+DR+ T cells and is reversed by allowing T cells to rest in culture: arguments for in vivo CD4+ T cell activation.

In HIV infection, several arguments suggest a certain degree of CD4+ T cell activation which might contribute to lymphocyte dysfunctions. To investigate this possibility, we determined the phenotypes of circulating CD4+ T cells using monoclonal antibodies directed to activation markers and examined whether the defective in vitro interleukin-2 (IL-2) production by purified CD4+ T cells isolated from infected individuals was reversible in rested cultured T cells, a phenomenon suggestive of in vivo CD4+ T cell exhaustion. The number of CD4+ T cells expressing HLA-DR molecules was the same as that observed in controls, remained constant throughout the course of HIV infection, and constituted a major part of circulating CD4+ T cells. In CDC stage II group, the increased percentage of CD4+DR+ T cells was also associated with an increased expression of early activation markers. Defective IL-2 production in vitro was restored when CD4+ T cells were allowed to rest in culture. In addition, the number of circulating CD4+DR+ T cells correlated negatively with the in vitro IL-2 production induced by phytohemagglutinin and phorbol ester by freshly isolated CD4+ T cells. Taken together, these data suggest that in vivo activated CD4+ T cells may participate in the immune abnormalities of HIV infection.

Antibodies, Monoclonal↗