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Biomedical subjects

G Fóris

Publications and source records attributed to G Fóris.

At least 37 records · Page 2Linked to original sources

Concentration-dependent effect of met-enkephalin on human polymorphonuclear leukocytes.

Met-enkephalin in 10(-9)-10(-7)M concentrations exerts an ADCC-stimulating effect on human PMNLs through naloxone-sensitive opiate receptors, elevating the cytoplasmic free Ca2+ and cGMP levels. In higher, 10(-6)-10(-5)M concentrations ME has a cAMP-elevating effect and a rapid 45Ca2+ influx was observed. This latter effect of ME, which is also associated with the suppression of ADCC activity, was abolished by the enkephalinase inhibitor, puromycin. A strong relationship is suggested between the suppressing effect of metenkephalin, enkaphalinase and the protein kinase C system.

Antibody-Dependent Cell Cytotoxicity↗

Bidirectional effect of met-enkephalin on macrophage effector functions.

Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10(-9)-10(-7)M) antibody dependent cellular cytotoxicity (ADCC) was markedly stimulated with a simultaneous decrease of Fc gamma receptor (Fc gamma R) medicated phagocytosis while the opposite was observed at 10(-6)-10(-5)M concentrations. Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na+ influx which was followed by a Ca2+ efflux in the range of low concentrations. In the range of high concentrations Na+ influx was accompanied by a Ca2+ influx. (2) ME at 10(-8) M concentration induced a rise in cGMP level with a plateau in the 60-120th min of incubation. This effect was prevented by 10(-5) M of naloxone. At 10(-6) M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10(-6) M abolished both the Ca2+ influx and the rise in cAMP level induced by 10(-6)-10(-5) M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10(-6)-10(-5) M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca2+ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase.

Adenylyl Cyclases↗

Age-dependent variations of intralysosomal enzyme release from human PMN leukocytes under various stimuli.

The intralysosomal beta glucuronidase and elastase release from polymorphonuclear leukocytes (PMNL) of young and aged male subjects were determined after 60-min incubation with 10 micrograms/ml Cytochalasin B (CB), 10(-6) M of Ca ionophore A 23187 and various concentrations of human low density lipoprotein (LDL). The beta glucoronidase secretion was triggered by both A 23187 and LDL; however, no significant differences were found between the enzyme release from PMNLs of young and aged subjects. In contrast, a marked elastase release was triggered in the young group only by LDL, whereas in the aged group, all of the applied drugs induced a significant elastase release. LDL caused the most dramatic enzyme release from PMNLs of aged males. It was concluded that the release of PMNL-elastase after LDL incorporation as well as by CB and Ca ionophore stimulation may be an age-related process.

Adolescent↗

A possible competition between 5'-monodeiodination of thyroxine and the respiratory burst in human granulocytes.

Thyroxine (T4) pretreatment of A 23187-stimulated human granulocytes in 10(-5)-10(-6) M concentration range inhibited the superoxide anion production of these cells. T4 increased the level of oxidized form of glutathione, whereas the intracellular level of the reduced form decreased. A similar alteration in the ratio of the oxidized to reduced forms of glutathione was detected in granulocytes during yeast cell phagocytosis. In addition, conversion of T4 to triiodothyronine (T3) was also inhibited during phagocytosis. A possible competition between 5'-monodeiodination of T4 and the oxidative burst of human granulocytes is discussed.

Adult↗

Immunomodulating effect of low density lipoprotein on human monocytes.

Low density lipoprotein (LDL) isolated from sera of healthy volunteers in 50 micrograms protein/ml concentration induced an early adenylate cyclase activation in human monocytes followed by elevation of cGMP level. In addition, a rapid 45Ca2+ influx was also detected on addition of 25-100 micrograms protein/ml concentrations. The monocyte activating effect of LDL under in vitro circumstances was characterized by an enhanced O2 consumption, H2O2 generation and by the increased release of lysosomal enzymes such as beta-glucuronidase and elastase like protease (ELP). On the other hand, LDL diminished markedly the Fc gamma receptor (Fc gamma R) mediated rosette formation, phagocytosis and the antibody dependent cellular cytotoxicity (ADCC) of monocytes without a significant decrease in the IgG binding capability of cells. High levels of serum LDL may play a significant role in the arterial wall injury by elastase like protease as well as biologically active oxygen species released from monocytes of patients suffering from arteriosclerosis.

Adult↗

The mechanism of antibody-dependent cellular cytotoxicity stimulation by somatostatin in rat peritoneal macrophages.

Somatostatin (SS) in 10(-9)-10(-7) M concentrations stimulated the lysis and inhibited the incorporation of IgG2a-coated 51Cr-labeled sheep red blood cell (SRBC) by rat peritoneal macrophages (PM). The intracellular killing capacity of PM remained unchanged. The enhancement of Fc receptor (R) activity and generation of active oxygen species were found to be responsible for the antibody-dependent cellular cytotoxicity (ADCC)-stimulating effect of SS. It was demonstrated that the stimulation of ADCC was abolished by the calmodulin inhibitor trifluoperazine (TFP), whereas it proved to be independent of the Ca2+ uptake. In addition, SS in the ADCC-stimulating concentrations diminished the intracellular cAMP generation and progressively increased the cGMP level. In higher (10(-6)-10(-7) M) concentrations, SS had a controversial effect on PM: it inhibited ADCC through the activation of both the adenylate cyclase and Ca2+ influx.

Animals↗

Age related variations of some polymorphonuclear leukocyte functions.

The age-related alterations of some biochemical processes in polymorphonuclear leukocytes (PMNL) obtained from 20 healthy aged male and 20 healthy aged female (age: 60-94 years) subjects were investigated. The basic level of luminol dependent chemiluminescence (LDCL) was increased, whereas the basal value of reduced/oxidized glutathione (GSH per GS-SG) was decreased in the aged groups. The enhancement of LDCL was more significant by PMNLs of aged males than of females. The change of both GSH and GS-SG levels during phagocytosis were diminished in the PMNLs of aged subjects. The L-alanine beta-naphthylamide specific elastase like protease (ELP) activity measured in living cell suspension was markedly increased with aging in male subjects. Therefore, it was concluded that the aging of PMNLs is partly a sex related process. The intensive release of both beta-glucuronidase (beta-G) and ELP by the PMNLs of aged subjects after in vitro treatment with calcium ionophore A23187, Cytochalasin B or low density lipoprotein (LDL) suggests that they could play an important role in some age-related disorders.

Adult↗

Body composition in elderly people. I. Determination of body composition by multiisotope method and the elimination kinetics of these isotopes in healthy elderly subjects.

The body composition of 40 healthy elderly and 20 healthy young subjects was determined and compared. It was found that the age-related changes were more marked in females than in males. Total body water was decreased as a consequence of diminished lean body mass. Extracellular fluid volume remained unchanged, while plasma volume increased. Thus, the liquid components of lean body mass were redistributed between the intracellular and extracellular spaces. The elimination kinetics of isotopes were not significantly different between young and aged subjects, except the elimination of radiosulfate.

Aged↗

Body composition in elderly people. II. Comparison of measured and predicted body composition in healthy elderly subjects.

The predictive values of the equations of Moore et al. and Hume and Weyers and the measured values of body composition were compared in healthy, carefully selected aged and young subjects of both sexes. In the case of young subjects, these prediction equations seem to be adequate, even if this could not be affirmed with certainty by our results. The equations of Moore et al. were found not to be adequate for elderly males, while they were only suitable for the determination of intracellular components in elderly females.

Adult↗

Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes.

Changes in the effector functions in polymorphonuclear leucocytes (PMNL), harvested from blood of young and aged healthy subjects of both sexes, were studied. FC gamma-receptor (Fc gamma R)-mediated incorporation of IgG coated 51Cr-HRBC significantly increased in the aged male group, while the phagocytosis of pre-opsonized fungi (Saccharomyces cerevisiae and Candida albicans) was independent of both the age and sex. However, the intracellular killing capacity of neutrophils obtained from aged male subjects significantly decreased toward 51Cr-labelled c. albicans. The antibody-dependent cellular cytotoxicity (ADCC) was also impaired with ageing in both sexes. The age-dependent decrease in the effector functions of PMNL may be explained, among others, by the fact that during yeast cell incorporation the increased cAMP level does not return to the basic level in the old group. On the other hand, the cGMP level which increased in PMNL of aged subjects does not show any progressive increase as in the young subjects, but remains unchanged. The oxidative metabolism producing free radicals being necessary for the effective intracellular killing and ADCC diminished in PMNL of aged subjects of both sexes. The above findings indicate that the adaptation of cyclic nucleotide system and the oxidative burst to the cell activation becomes impaired with ageing.

Adult↗

Age-related changes in cAMP and cGMP levels during phagocytosis in human polymorphonuclear leukocytes.

Alterations of cyclic nucleotides have been studied during the incorporation of opsonized yeast cells into human polymorphonuclear leukocytes (PMNL) from both young and aged subjects. In PMNLs obtained from healthy young males the cAMP level rose to a maximal value during the first 15 min and returned to the starting level at the 60th min of phagocytosis. The cGMP level started to rise only at the 30th min of incorporation and enhanced progressively up to the 120th min. In contrast, the elevated cAMP level remained increased during the 120 min of phagocytosis in PMNLs obtained from aged subjects, whereas the cGMP level was not altered during the same period. The basic level of cAMP diminished, while the cGMP level was found to be elevated with ageing in PMNLs. It is concluded that phagocytosis was not impaired with age yet cytotoxic functions were diminished and that the data presented support the idea that cyclic nucleotides may be directly involved only in the latter process.

Adolescent↗

Interrelation between body composition and endocrine system in healthy elderly people.

The body composition of 40 healthy aged and 20 healthy young people was determined using a multi-isotope method. At the same time their hormonal status was assessed. A correlation between the body composition and the endocrine status was investigated. Our results concerning the body composition and the hormonal values correlate with the findings of the literature. A strong correlation was found between the plasma volume and the renin-angiotensin-aldosterone system. The interrelation could explain the reciprocal age related changes of plasma volume and the renin-angiotensin-aldosterone system. No or weak correlation could be found between the body composition and other measured hormones.

Adult↗

Met-enkephalin induced alterations of macrophage functions.

Met-enkephalin /Met-enk/ was found to stimulate IgG2a-mediated antibody dependent cytotoxicity /ADCC/ of thioglycollate elicited rat peritoneal macrophages /PM/ through naloxone-sensitive opiate receptors in concentrations ranging from 10(-9) - 14(-7) M. Phagocytosis of IgG2a coated 51Cr-sheep red blood cell /SRBC/ was suppressed by M-enk in the same concentration range. In the same range of concentrations, M-enk was observed to induce a significant increase in the generation of luminol dependent chemiluminescence /LDCL/. The observed stimulation of ADCC was abolished by calmodulin inhibitor triflouroperazine /TFP/ in 10(-6) M concentration. The involvement of cyclic nucleotides in the M-enk induced functional alterations is indicated by finding cGMP accumulation to be augmented in M-enk treated PMs.

Animals↗

Regulation of Fc mu receptor-mediated functions of resident and provoked peritoneal macrophages.

Modifying and/or regulating effects on Fc mu receptor (R) mediated phagocytic and ADCC activity of both resident (r) and provoked (p) peritoneal macrophages (PM) was studied applying drugs affecting the cytoskeleton and cation transport. In addition, the effects of exogenous PGE2 and cyclic nucleotides were also examined. Fc mu-receptors appear to be functionally less significant in provoked PMs than in resident ones since both Fc mu-receptor mediated phagocytosis and ADCC were lower in the formers. The cytoskeletal system is important in the regulation of both Fc mu-receptor-mediated functions. Phagocytosis through Fc mu-receptor is decreased by Cytochalasin B and by Vinblastine treatment, whereas ADCC is enhanced by Cytochalasin B. Extracellular PGE2 and cAMP induced a higher phagocytic activity and suppressed ADCC, whereas cGMP displayed an opposite effect. The sensitivity of Fc mu R-mediated activities to ionophoric and to cytoskeleton-damaging drugs was lower in provoked than in resident PMs. In addition, the regulatory role of PGE2 and of cyclic nucleotides on the same activities was less marked on provoked PMs. In contrast, ouabain inhibits Fc mu R-dependent antigen incorporation and ADCC on provoked PM monolayers only. These findings suggest differing regulatory mechanisms for Fc mu R-mediated functions in provoked PMs as compared with resident ones.

Animals↗

Ionophore-induced functional changes in macrophages.

Ca ionophore A 23187 and valinomycin known to induce Ca2+ influx, i.e. K+ efflux, appeared to induce activation-related changes in rat peritoneal macrophages (PM) at 10(-5)-10(-7) M concentrations as revealed by aggregation, nitro blue tetrazolium (NBT) reduction, superoxide anion production as well as beta glucuronidase release; however, lactate dehydrogenase (LDH) activity was measured in supernatants only after treatment with 10(-5) M of A 23187. The PM-activating effect of A 23187 was abolished in the presence of 5 mM EGTA, whereas the activating effect of K ionophore did not depend on the extracellular Ca2+. Fc receptor (FcR) mediated incorporation, intracellular killing as well as the antibody dependent cytotoxicity (ADCC) were markedly inhibited upon incubation with Ca ionophore or valinomycin. C3bR mediated phagocytosis was found to be more resistant to the cation transport affecting drugs. The impairment of effector functions was elicited by nontoxic concentrations of ionophores, however, their inhibiting effects did not require extracellular Ca2+ at the time of ionophore-exposition.

Animals↗

Age-dependent changes of the Fc gamma-receptor-mediated functions of human monocytes.

The age-dependent alterations of phagocytosis and age-dependent cell change (ADCC) activity through Fc gamma receptors of human monocyte monolayers using anti-D human IgG-coated 51Cr-labeled human red blood cells were determined. 40 healthy aged subjects of both sexes (age: 60-85 years) and 20 healthy young people of both sexes (age: 18-25 years) were studied. The phagocytosis increased significantly with aging in both sexes, whereas a decrease in ADCC activity was found.

Adolescent↗

Effects of urethan on lymphokine-producing activity of lymphocytes and on some functions of peritoneal macrophages in rats.

Effects of urethan on some functions of blood lymphocytes and peritoneal macrophages (PMs) of rats were studied in in vivo and in vitro experiments. The in vitro lymphokine (LK) producing activity of lymphocytes in the presence of specific antigen was depressed by urethan administered 1-5 days before the BCG sensitization. However, the drug injected after the BCG sensitization was not effective on the LK production. Urethan added to the cultures of previously BCG-primed lymphocytes did not influence the LK production. The sensitivity of glycogen-provoked PMs (pPM) to LK-induced activation and, at the same time, the 125I-IgG2a binding capacity as well as the EA rosette formation of the provoked PMs were depressed by urethan administered 1-5 days before the lavage of PMs. These functions of resident PMs (rPM) were not altered by the drug treatment. Urethan added to the cultures of resident or provoked PMs proved to be ineffective. These results led to the conclusions that urethan, after its in vivo metabolic conversion, causes an impairment of the macrophage functions in the inductive phase of the immune response and this event may be the crucial point in the immunosuppressive effect of urethan.

Animals↗