Search PubMed⌕ Search

Biomedical subjects

T Bengtsson

Publications and source records attributed to T Bengtsson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Childhood misery and disease in later life: the effects on mortality in old age of hazards experienced in early life, southern Sweden, 1760-1894.

This paper assesses the importance of early-life conditions relative to the prevailing conditions for mortality by cause of death in later life using historical data for four rural parishes in southern Sweden for which both demographic and economic data are very good. Longitudinal demographic data for individuals are combined with household socio-economic data and community data on food costs and the disease load using a Cox regression framework. We find strong support for the hypothesis that the disease load experienced during the first year of life has a strong impact on mortality in later life, in particular on the outcome of airborne infectious diseases. Hypotheses about the effects of the disease load on mothers during pregnancy and access to nutrition during the first years of life are not supported. Contemporary short-term economic stress on the elderly was generally of limited importance although mortality varied by socio-economic group.

Aged↗
PubMed1999

Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils.

Oxidative stress induces apoptosis in many types of cells, including human neutrophils. Our objective was to determine whether reactive oxygen species (ROS) produced by activated neutrophils are associated with accelerated apoptosis. Exposing neutrophils to ionomycin or phorbol myristate acetate (PMA) induced intracellular H2O2 production and rapid onset of apoptosis, measured as condensed chromatin, cellular shrinkage, and DNA fragmentation. Neutrophils activated with formyl-methionyl-leucyl-phenylalanine (fMLP) generated mainly extracellular H2O2 and did not undergo apoptosis. Exogenously added H2O2, together with the catalase blocker sodium azide, induced apoptosis to the same extent and with similar kinetics as PMA and ionomycin. Adenosine inhibited ionomycin-induced intracellular H2O2 production and apoptosis. Neither PMA nor ionomycin caused apoptosis in dimethyl sulfoxide-differentiated HL-60 cells, which are incapable of intracellular H2O2 production, whereas H2O2 induced apoptosis more efficiently in these cells than in neutrophils. We propose that activated neutrophils use intracellularly formed H2O2 to commit suicide.

Apoptosis↗
PubMed1999

Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists.

BACKGROUND: Anti-obesity effects of calcium antagonists such as benidipine and nifedipine have been described in rodent obesity models, but the mode of action of the calcium antagonists as anti-obesity agents has not been established. OBJECTIVE: To examine whether the anti-obesity effects of calcium antagonists (here benidipine) could be ascribed to a direct stimulation of brown adipose tissue (BAT) thermogenesis. METHODS: Examination of the ability of benidipine to induce thermogenesis (increased rate of oxygen consumption) in isolated brown-fat cells from rats, mice and hamsters--and in intact cold-acclimated rats. RESULTS: Benidipine itself, or in combination with any dose of noradrenaline (NA), was totally unable to induce or augment thermogenesis in isolated brown-fat cells of any species tested. However, it markedly induced thermogenesis in intact animals (approx 60% increase over resting metabolic rate). This effect could be fully inhibited by propranolol. CONCLUSION: Benidipine is itself without thermogenic effect. The thermogenic response in-vivo (and thus presumably the anti-obesity effect) is probably secondary to a previously described general side-effect of calcium antagonists: a release of NA from sympathetic nerves, here most likely directly from nerves in the BAT. The anti-obesity effect of benedipine is thus probably not due to its calcium channel blocking effect. PERSPECTIVES: It is probable that the anti-obesity effects of calcium antagonists reported in several models of genetically obese rodents (MSG-obese and agouti mice, SHHF/Mcc-fa(cp) and JCR:LA-corpulent rats) are mediated via an indirect stimulation of BAT. To what extent calcium antagonists may induce similar effects in a clinical situation, is currently unknown.

Adipose Tissue, Brown↗
PubMed1999

Platelets enhance neutrophil locomotion: evidence for a role of P-selectin.

It has been suggested that the accumulation of platelets at sites of vascular damage and inflammation regulates the function of leukocytes. In this study, we investigated the effects of platelets on the transmigration of neutrophil granulocytes through microporous membranes. We demonstrate that platelets markedly enhance both the random and the chemotactic migration of neutrophils. Stimulatory effects were acquired by adding paraformaldehyde-fixed platelets or the supernatants of platelets; however, the effects were lower or significantly higher, respectively, compared with viable platelets. The increased neutrophil migration was associated with an amplified polymerization of actin filaments and expression of CD11b/CD18. Previous investigations indicate that the initial adhesion between platelets and neutrophils is mediated by P-selectin exposed on the surface of platelets. In this study, the following observations suggest a role for P-selectin in the platelet-induced enhancement of neutrophil motility: (i) platelet supernatants contained substantial amounts of P-selectin, (ii) filtration of platelet supernatants markedly reduced the content of P-selectin and simultaneously decreased the potentiating effects on neutrophil motility, (iii) inhibition of P-selectin-mediated cell cell adhesion with sialyl Lewis X or by incubation in calcium-free medium reduced the enhancing effects of platelets on neutrophil responses, and (iv) purified and recombinant P-selectin mimicked the effects of platelets on neutrophil locomotion. In conclusion, we propose that platelets through P-selectin promote accumulation and emigration of neutrophils during inflammatory and thrombotic processes.

Actins↗
PubMed1999

beta1 to beta3 switch in control of cyclic adenosine monophosphate during brown adipocyte development explains distinct beta-adrenoceptor subtype mediation of proliferation and differentiation.

To explain the distinctive pharmacological profiles observed for adrenergic stimulation of cell proliferation (beta1) and cell differentiation (beta3), the adrenergic control of cAMP accumulation was investigated during brown adipocyte development. In preadipocytes, norepinephrine (NE) increased cAMP levels but the beta3-agonists BRL-37344 and CGP-12177 did not; in contrast, when the cells had differentiated into mature brown adipocytes, a large cAMP response to the beta3-agonists had emerged and was now double that to NE (although the affinity of NE had increased 10-fold). Beta1-messenger RNA (mRNA) levels were high in both pre- and mature brown adipocytes; beta3-mRNA did not appear until maturation but then abruptly. Although beta1-receptors remained detectable by [3H]CGP-12177 binding in the mature brown adipocytes, the cAMP response to NE (based on propranolol inhibitory potency) switched from beta1 to beta3. Even the established beta1-agonist dobutamine acted through beta3-receptors in the mature brown adipocytes. The increases in cAMP levels could adequately explain the increased cell proliferation in NE-stimulated preadipocytes and the NE-induced UCP1 gene expression in mature brown adipocytes. The distinctive adrenergic profiles for stimulation of proliferation and of differentiation were thus not due to the existence of additional pathways but to a switch in the type of beta-receptor mediating the NE response, coordinated with an alteration in the nuclear response to increased cAMP levels. The study implies that full recruitment of brown adipose tissue cannot be induced by exclusive beta3-stimulation.

Adipocytes↗
PubMed1998

Modulation of the chemotactic peptide- and immunoglobulin G-triggered respiratory burst in human neutrophils by exogenous and endogenous adenosine.

The effects of exogenous and endogenous adenosine on the production of oxygen metabolites in neutrophils triggered by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) or immunoglobulin G (IgG)-opsonized yeast particles, were investigated. By using luminol-enhanced chemiluminescence, we found that adenosine A1 receptor activation did not affect, whereas adenosine A receptor activation, through a mechanism involving the cyclic AMP (cAMP)-protein kinase A signalling pathway, both inhibited the fMLP- and IgG-triggered respiratory burst. The adenosine-induced inhibition was however more pronounced after exposure to fMLP than to IgG-yeast. Stimulation with fMLP caused an extracellular accumulation of endogenous adenosine, which indicates that this event is a negative-feedback mechanism preventing an uncontrolled activation of chemoattractant-stimulated neutrophils. On the contrary, exposure of neutrophils to IgG-yeast did not appear to accumulate extracellular adenosine, probably due to increased adenosine deaminase activity during phagocytosis. In conclusion, this work accentuates the importance of adenosine, both exogenously applied and endogenously formed, as an inflammatory agent modulating the respiratory burst during the different phases in neutrophil activation.

Adenosine↗
PubMed1998

Adenosine inhibits actin dynamics in human neutrophils: evidence for the involvement of cAMP.

The mechanisms by which adenosine regulates the inflammatory reaction are poorly characterized. In this study, we investigated the effects of adenosine on neutrophil actin polymerization elicited by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) or IgG-opsonized yeast particles. We used bodipy-phallacidin staining in combination with flow cytometry and found that adenosine markedly reduced actin polymerization triggered by IgG-yeast, whereas the effect on the fMLP-response was less pronounced. Similar or even more pronounced effects were obtained with the adenosine A2 receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA), suggesting an A2 receptor-mediated mechanism. The following observations indicate that the A2 receptor-induced effects involve the cAMP-protein kinase A (PKA) signaling pathway: (1) a combination of NECA and the cAMP-specific phosphodiesterase (PDE) inhibitor Ro 20-1724 raised the cAMP content in both unstimulated and stimulated neutrophils and also further inhibited the actin dynamics; (2) the PKA inhibitor H89 reversed the inhibitory effects of NECA on the actin dynamics; (3) Ro 20-1724, isoproterenol and dibutyryl cAMP (DBcAMP) reduced actin polymerization in almost the same way as NECA did. NECA together with Ro 20-1724 impaired the fMLP-induced shape changes and cortical accumulation of actin filaments. In contrast, H89 potentiated the fMLP-induced formation of a submembranous ring of actin filaments. Neutrophils phagocytosing yeast particles in the presence of NECA and Ro 20-1724 were predominantly round in shape, and their ability to extend actin-rich pseudopods around the prey was reduced. These effects were partly antagonized by H89. In correlation with the effects on actin polymerization, NECA more effectively diminished IgG-induced upregulation of the beta2 integrin CD11b/CD18 than such upregulation induced by fMLP. The inhibitory effects of A2-receptor activation on actin dynamics and beta2 integrin expression in neutrophils exposed to IgG-yeast were also associated with a cAMP-dependent reduction of the phagocytic capacity. In conclusion, we show that adenosine inhibits actin dynamics and shape changes in neutrophils via a cAMP-dependent pathway. This finding further characterizes the mechanisms by which adenosine functions as an important modulator of the inflammatory response.

Actins↗
PubMed1998

Immunological findings in blood and bronchoalveolar lavage fluid in chronic bronchitis patients with recurrent infectious exacerbations.

Bronchial infections are common in smokers and seem to be related to the presence of chronic bronchitis (CB). Why only some smokers develop repeated bronchial infections is not known. The aim of this study was to screen for immunological changes associated with disease in patients with CB and recurrent infectious exacerbations compared to asymptomatic smokers. Sixteen smokers with stable CB and recurrent infectious exacerbations, and 18 asymptomatic smokers, all without any immunomodulating treatment, underwent bronchoscopy and bronchoalveolar lavage (BAL). Smoking history and current smoking status were comparable. Serum levels of immunoglobulin (Ig)A, IgM, IgG and IgG subclasses were measured. Blood and BAL lymphocyte phenotypes and proliferative responses of peripheral blood mononuclear cells (PBMCs) to various stimulators were analysed. Unstimulated and tetanus toxoid-stimulated production of cytokines in PBMC cultures was measured. Natural killer (NK-) cell activity was analysed. A significantly (p<0.05) lower level of IgG3 was found in the CB group, and a significantly (p<0.01) higher proliferative response of PBMCs was found in the CB group after stimulation with diphtheria toxoid. Detectable levels of interleukin (IL)-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma, but not of IL-2, IL-4 or transforming growth factor-beta2, were found in supernatants from cultured cells in both study groups. Stimulated TNF-alpha production was significantly (p<0.05) higher in the CB group. NK-cell activity did not differ significantly between the study groups. There were no major differences between the groups in lymphocyte subpopulations in blood or BAL. In conclusion, no major alterations in the analysed indices of cell-mediated and humoral immunity were found in patients with chronic bronchitis prone to recurrent infectious exacerbations when compared with asymptomatic smoking controls.

Adult↗
PubMed1996

Down-regulation of beta3 adrenoreceptor gene expression in brown fat cells is transient and recovery is dependent upon a short-lived protein factor.

The regulation of the expression of the beta3 adrenoreceptor gene was examined in the brown adipose tissue of intact mice and in murine brown fat primary cell cultures. Both in vivo and in vitro, high levels of beta3 receptor mRNA were observed. Acute cold exposure of mice resulted in a marked and rapid down-regulation of beta3 gene expression; this down-regulation was, however, transient. Similarly, in brown fat cell cultures, norepinephrine addition led to down-regulation of beta3 gene expression, with a lag phase of 30 min and with an apparent half-life of beta3 mRNA of approximately 30 min. This down-regulation was stimulated via the beta3 receptors themselves and mediated via cAMP; the apparent affinity of norepinephrine was extremely high (<1 nM). The degradation rate after actinomycin was identical to that after norepinephrine and was not affected by the presence of norepinephrine; thus, the down-regulation was due to cessation of transcription but not to an increased rate of degradation. Notably, inhibition of protein synthesis by cycloheximide also led to down-regulation. The norepinephrine-induced down-regulation was transient; spontaneous recovery occurred after approximately 18 h and was not due to depletion of adrenergic agent. Recovery did not occur in the presence of cycloheximide. After recovery, the cells showed a functional desensitization of the down-regulation process itself (EC50 now approximately 10 nM). It is concluded that a down-regulated state cannot explain the functional desensitization of beta3 adrenergic responsiveness observed in brown fat cells isolated from cold-acclimated animals (i.e. physiologically chronically adrenergically stimulated brown fat cells); since the beta3 receptor is not subject to desensitization via phosphorylation processes, no satisfactory explanation for the functional desensitization exists as yet. A model is presented for the down-regulation/recovery process, involving the participation of a phosphorylatable short-lived transcription factor.

Adipose Tissue, Brown↗
PubMed1996

Sulfatide-induced L-selectin activation generates intracellular oxygen radicals in human neutrophils: modulation by extracellular adenosine.

The sulfated form of galactocerebrosides (sulfatides) have recently been established as ligands for L-selectin. In this study we show that exposure of human neutrophils to sulfatides induces a transient generation of oxygen radicals, revealed by the luminol-enhanced chemiluminescence (CL) technique. The CL response was mainly located intracellularly, and was dependent on sulfation of the galactose ring, since non-sulfated galactocerebrosides had no effect. Sulfatides also dramatically amplified the CL response triggered by the chemotactic peptide formylmethionyl-leucyl-phenylalanine (fMLP). This effect was primarily due to an increased (up to 10-fold) intracellular generation of oxygen metabolites. Removal or blocking of L-selectin with chymotrypsin and monoclonal antibodies, respectively, markedly reduced the effects of sulfatides. Furthermore, sulfatides amplified the CL response triggered by ionomycin, whereas the response induced by phorbol-12-myristate-13-acetate was slightly reduced. The tyrosine kinase inhibitor, genistein, markedly inhibited the oxygen radical production induced by sulfatides, and totally abolished the potentiating effects of sulfatides in fMLP- and ionomycin-stimulated neutrophils. Sulfatides also triggered a transient rise in the intracellular free calcium concentration, [Ca2+]i. Consequently, L-selectin activation through sulfatides appear to affect oxidase activity through a Ca(2+)-dependent pathway involving tyrosine phosphorylation. Adenosine is an anti-inflammatory agent predominately released from the vascular endothelium which might suppress an inappropriate activation of the oxidase during L-selectin-mediated rolling of neutrophils. Indeed, we found that adenosine inhibited the oxidative burst induced by sulfatides, mainly by attenuating the intracellular generation of oxygen radicals. However, 10-100 times higher concentration of exogenous adenosine was required to inhibit the CL response induced by sulfatides to the same extent as the adenosine-mediated inhibition of the fMLP-induced response. This difference in sensitivity to adenosine could be explained by various expression of extracellular adenosine deaminase (ADA), since we found that the ADA-inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) markedly reduced the oxygen radical production caused by sulfatides and almost totally abolished the potentiating effects of sulfatides on the fMLP-induced respiratory burst. In contrary, EHNA only slightly reduced the fMLP-triggered CL response. We suggest that the initial activation of L-selectin prepare the neutrophil for an effective microbicidal activity in the extravascular space. This process might be dependent on a L-selectin-mediated increase in the expression and activity of ADA, which locally reduces the extracellular level of adenosine.

Adenosine↗
PubMed1996

Release of oxygen metabolites from chemoattractant-stimulated neutrophils is inhibited by resting platelets: role of extracellular adenosine and actin polymerization.

The effect of human platelets on chemoattractant-induced generation of oxygen metabolites in neutrophils was investigated, using luminol-enhanced chemiluminescence (CL). Resting platelets inhibited the extracellular, but not the intracellular, production of oxygen radicals in formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe)-stimulated neutrophils. Maximal effect was obtained at the physiological neutrophil/platelet ratio of 1/50. Similar results were acquired by adding supernatants of platelets, indicating a role for a soluble factor. Removal of extracellular adenosine by adenosine deaminase (ADA), or blocking of adenosine-receptors by theophylline, antagonized the inhibitory effects of platelets (or the equivalent supernatant) on the neutrophil respiratory burst. In contrast, accumulation of adenosine by apyrase enhanced the inhibition. Exogenous adenosine mimicked the effects of platelets on the fMet-Leu-Phe-induced respiratory burst. To further assess the role of platelet-derived adenosine, the platelets were fixed with paraformaldehyde. We found that fixed platelets, as well as their supernatant, inhibited the fMet-Leu-Phe-induced CL-response to the same extent as viable cells. These effects were also reversed by ADA and theophylline, respectively. A prior removal of adenosine in the platelet suspension by ADA, followed by treatment with erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) to inactivate ADA, did not reverse the inhibitory action of platelets on the fMet-Leu-Phe-induced CL-response in neutrophils. However, if adenosine receptors of neutrophil at the same time were blocked with theophyline, the inhibition was significantly reduced. Platelets markedly increased the generation of adenosine in a neutrophil suspension. The effect was antagonized by S-(4-Nitrobenzyl)-6-thioguanosine (NBTG), but unaffected by alpha, beta-methyl-eneadenosine5'diphosphate (AMP-CP), indicating that the platelet-dependent accumulation of adenosine is due to an increased release of endogenous adenosine from neutrophils and not to a degradation of extracellular AMP. In correlation, NBTG, but not AMP-CP, reversed the platelet-mediated inhibition of the fMet-Leu-Phe-induced CL-response in neutrophils. Consequently, these data suggest that a platelet-derived factor increases the release of endogenously formed adenosine from neutrophils, terminating the production of oxygen radicals. The inhibition of oxidase activity was also associated with a platelet-induced polymerization of actin in the margin of the neutrophils. Treatment of neutrophils with cytochalasin B reversed the effects of platelets, both on F-actin content and CL-response. In summary, resting platelets limit the release of oxygen radicals from chemoattractant-stimulated neutrophils, thus preventing excessive damage to host tissues in the vascular space. This effect is suggested to be associated with an increase generation of neutrophil-derived adenosine enhancing an autoregulatory inhibitory pathway, and a peripheral accumulation of actin filaments forming a barrier for extracellular release of reactive oxygen radicals.

Actin Cytoskeleton↗
PubMed1996

Platelets enhance Fc(gamma) receptor-mediated phagocytosis and respiratory burst in neutrophils: the role of purinergic modulation and actin polymerization.

The interaction of platelets with neutrophil granulocytes is considered to play an important role in the inflammatory process, and the present study was focused on platelet-induced modulation of Fcgamma receptor-mediated functions in neutrophils. We found that phagocytosis and the respiratory burst (measured as luminol-enhanced chemiluminescence), triggered in neutrophils by immunoglobulin G (IgG)-opsonized yeast particles, were potentiated by platelets and that maximal enhancement was achieved at a physiological neutrophil/platelet ratio of about 1:50 to 1:100. Platelets both increased the intra- and extracellular generation of oxygen radicals as well as the release of myeloperoxidase from stimulated neutrophils. The presence of platelets also induced a cortical actin polymerization in neutrophils, which might explain the increased phagocytic capacity. Platelets appear to affect neutrophil function in a contact-independent manner that most likely involves ATP, indicated by the following: (1) platelet supernatants, but not fixed platelets, affected neutrophil function in the same way as viable platelets; (2) platelets raised the extracellular ATP level four- to fivefold; (3) exogenous ATP mimicked the effects of platelets on actin polymerization, phagocytosis, and the respiratory burst in neutrophils; (4) hydrolysis of extracellular ATP with apyrase or blocking of ATP receptors with suramin reversed the platelet-induced enhancement of neutrophil function. An increased accumulation of extracellular adenosine, induced by inhibiting endogenous adenosine deaminase or adding exogenous adenosine, reversed the effects of platelets. The platelet-induced potentiation of the respiratory burst was inhibited by the tyrosine kinase inhibitor genistein, suggesting that tyrosine phosphorylation is involved. However, platelets did not significantly affect the Fcgamma receptor-triggered calcium response in neutrophils. In conclusion, we show that platelets, through an ATP-dependent mechanism, potentiate IgG-mediated ingestion and production of oxygen metabolites in neutrophils.

Actins↗
PubMed1996

Synergistic inhibition of thrombin-induced platelet aggregation by the novel nitric oxide-donor GEA 3175 and adenosine.

1. The influence of the novel nitric oxide-donor GEA 3175 on thrombin- and ionomycin-stimulated human platelets was investigated. The effect of GEA 3175 was compared with that of adenosine, an activator of platelet adenylyl cyclase. 2. GEA 3175 inhibited thrombin-induced secretion of ATP but did not affect aggregation; similar results were obtained with adenosine. 3. Thrombin-stimulated rises in the cytosolic free Ca2+ concentration, [Ca2+]i, were dose-dependently inhibited by GEA 3175 and adenosine. GEA 3175 and adenosine maximally reduced the initial rise in [Ca2+]i by 41% and 35%, respectively. 4. Simultaneous exposure to GEA 3175 and adenosine nearly abolished both the functional responses (i.e. aggregation and degranulation) and the rises in [Ca2+]i in thrombin-stimulated platelets. 5. Aggregation and increases in [Ca2+]i triggered in platelets by the Ca(2+)-ionophore ionomycin were only marginally affected by a combination of GEA 3175 and adenosine. 6. GEA 3175 potently increased the guanosine 3':5'-cyclic monophosphate (cyclic GMP) content in platelets but did not affect adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels. Adenosine did not increase either the cyclic AMP or the cyclic GMP levels in platelets. However, adenosine and GEA 3175 combined significantly elevated the platelet cyclic AMP content. 7. The results show that simultaneous exposure to GEA 3175 and adenosine promotes potent anti-aggregatory properties in platelets in vitro. The findings suggest that blockage of the cytosolic Ca(2+)-signal, which is probably mediated by an amplified cyclic nucleotide response, is an important event during the synergistic inhibition of thrombin-induced aggregation.

Adenosine↗
PubMed1996

Beta 3-adrenoceptor in guinea pig brown and white adipocytes: low expression and lack of function.

In the guinea pig, cold acclimation induced a conversion of unilocular to multilocular adipocytes in interscapular (IS) and retroperitoneal (RP) fat depots but not in the epididymal (EP) fat pad. The conversion was associated with an increase in mitochondriogenesis and the appearance of the uncoupling protein. The maximal lipolytic responses to norepinephrine and dibutyryl adenosine 3',5'-cyclic monophosphate were decreased in IS cells, unchanged in RP cells, and increased in EP cells, suggesting a site-specific regulation of lipolysis at the postreceptor level. beta 3-Adrenergic agonists were not lipolytic regardless of the depot and the thermal environment of the animal. These agents did not inhibit glucose transport and lipogenesis, as was previously reported for rodents. Cloning and sequencing of the guinea pig beta 3-adrenoceptor gene revealed a slightly higher amino acid sequence similarity with the human than with the rodent beta 3-adrenoceptors. beta 3-Adrenoceptor transcripts were present at a very low level in guinea pig adipocytes, and mRNA levels did not increase to a significant extent after cold acclimation. The guinea pig thus differs from rodents by an absence of beta 3-adrenergic effects and by low beta 3-adrenoceptor expression in brown and white adipose tissues.

Acclimatization↗
PubMed1995

Chemoattractant-induced NADPH oxidase activity in human monocytes is terminated without any association of receptor-ligand complex to cytoskeleton.

When the chemotactic peptide formylmethionyl-leucyl-phenylalanine binds to its cell surface receptor, a transmembrane signal is generated that activates the superoxide-producing NADPH oxidase of human phagocytes. Comparing monocytes and neutrophils with regard to the production of superoxide anion induced by the peptide, we found a similar time-course for both types of cells. In neutrophils, ligand binding induced a conversion of the receptor to a high-affinity form, a change suggested to be due to an association of the receptor-ligand complex to the Triton X-100-insoluble cytoskeleton. This event has been hypothesized to terminate the signal that activates the NADPH oxidase and thereby results in cessation of the cellular production of superoxide anion. Neutrophils preincubated with the cytoskeleton-disrupting drug cytochalasin B showed an increased and prolonged superoxide anion production after activation with the peptide, thus indicating that the cytoskeleton is involved in terminating this response. Formylmethionyl-leucyl-phenylalanine was also found to induce polymerization of actin in monocytes; however, cytochalasin B had no effect on the peptide-induced generation of superoxide anion in these cells. Furthermore, also in monocytes, ligand binding induced a conversion of the receptor to a high-affinity form; however, the receptor-ligand complex did not coisolate with the Triton X-100-insoluble cytoskeleton. These results indicate that, in monocytes, the NADPH oxidase activating pathway is terminated without any association of the receptor-ligand complex to the Triton X-100-insoluble cytoskeleton.

Actins↗
PubMed1994

The role of cyclic AMP, calcium and filamentous actin in adenosine modulation of Fc receptor-mediated phagocytosis in human neutrophils.

The role of cyclic AMP, calcium and filamentous actin (F-actin) content during adenosine modulation of Fc receptor (FcR)-mediated phagocytosis in adherent human neutrophils was investigated. Phagocytosis of IgG-opsonized yeast particles was found to be enhanced by pico- to nanomolar concentrations of adenosine or the A1-agonist N6-cyclopentyl-adenosine (CPA) but reduced by micromolar concentrations of adenosine or the A2-agonist 5'-N-ethylcarboxamidoadenosine (NECA). NECA, in the presence of the cAMP-specific phosphodiesterase inhibitor Ro 20-1724, increased the intracellular content of cAMP during phagocytosis. Ro 20-1724 potentiated the NECA-induced reduction of the phagocytic capacity. These observations indicate that cAMP elevations are involved in A2-receptor-mediated inhibition of phagocytosis. NECA, in the presence of Ro 20-1724, markedly enhanced the action polymerization associated with adhesion to the substrate and contact with the phagocytic prey. During advanced phagocytosis, however, the F-actin content reached levels clearly below those observed in control cells. This prolonged depolymerization phase correlated with the A2-receptor-induced cAMP elevation. Depletion of intracellular free calcium abolished the cAMP-elevating effects of NECA, and also completely abrogated the A1- and A2-receptor-mediated effects on phagocytosis. However, since NECA reduced the F-actin content even in Ca(2+)-depleted cells, A2-receptor-mediated inhibition of phagocytosis could not be directly coupled to changes in the overall content of F-actin. Our results indicate that adenosine modulates FcR-mediated phagocytosis in a calcium-dependent way, and does so through 'stimulatory' A1 and 'inhibitory' A2 receptors, and also that cAMP elevation is linked to the A2-receptor-induced inhibition of phagocytosis.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1994

S-nitroso-N-acetylpenicillamine reduces leukocyte adhesion to type I collagen.

The initial step in the migration of neutrophils to the extravascular space is adhesion to the endothelium. We examined the effect of nitric oxide on this process by treating human neutrophils with S-nitroso-N-acetylpenicillamine (SNAP), a NO-producing compound. Since NO has been shown to increase the level of cGMP in other cell types, we used 8-Br-cGMP in order to mimic the effects of NO. Indeed, both these treatments resulted in a reduced adhesion of neutrophils to type I collagen coated surfaces. After a prolonged incubation with SNAP, the adhesion was the same as for untreated cells. SNAP incubation reduced the F-actin content in the cells whereas 8-Br-cGMP increased it, demonstrating different mechanisms of action on F-actin. These data suggest that endothelium-derived nitric oxide is an important endogenous modulator of neutrophil adhesion, but the effect is not mediated by a cGMP-dependent regulation of F-actin levels.

Actins↗