RESUMO
The differential sensitivity of peripheral blood granulocytes, monocytes, and lymphocytes to endotoxin-induced apoptosis was studied in convalescents with Salmonella infection. The number of early (Tunel+PI-) and late (Tunel+PI+) apoptotic cells and the rate of apoptosis (the relative content of DNA apoptotic fragments in the solitary cell) were determined on a FACSCalibur cytofluorometer, by applying a package of the CellQuest programs (Becton Dickinson). A higher threshold of sensitivity of granulocytes, monocytes, and lymphocytes to the apoptotic effect of low, suboptimal doses (100 ng), as well as suppression of early stages of apoptosis by the optimal doses (1000 ng) of S. enteritidis lypopolysaccharides (LPS) were observed in patients who had sustained salmonellosis at a stage of reconvalescence. The hierarchy of LPS-induced apoptosis (granulocyte--monocyte--lymphocyte), observed in healthy donors, was also retained in the group of patients receiving the suboptimal doses of LPS, which seems to be associated with the repeated action of toxin on sensitized cell populations.
Assuntos
Apoptose , Granulócitos , Linfócitos , Monócitos , Infecções por Salmonella/sangue , Adolescente , Adulto , Endotoxinas/farmacologia , Granulócitos/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Linfócitos/efeitos dos fármacos , Masculino , Monócitos/efeitos dos fármacosRESUMO
The in vitro induction of granulocytes in the presence of high and low concentrations of lipopolysaccharides (LPS) allowed the authors to study a dose-dependent apoptotic response in the population of intact cells and in that of primed cells in the period of convalescence in patients with Salmonella infection. An experimental system was used to study a respiratory burst and granulocytic apoptosis in the presence of hypothalamic neuropeptides. The clinical manifestations of the diseases were studied in 32 inpatients. It was shown that there was an increase in the sensitivity of granulocytes to the apoptotic action of low, suboptimal doses (100 ng) of S. enteritidis LPS in patients with salmonellosis at convalescence. This correlates with the severity of a clinical course of the experienced disease and with the suppressed sensitivity of apoptosis to the optimal doses (1000 ng) LPS.
Assuntos
Apoptose , Toxinas Bacterianas/toxicidade , Endotoxinas/toxicidade , Granulócitos/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Infecções por Salmonella/diagnóstico , Convalescença , DNA/análise , Fragmentação do DNA , Humanos , Ativação de Neutrófilo , Prognóstico , Explosão Respiratória , Índice de Gravidade de DoençaRESUMO
The effect of an endotoxin--E. coli liposaccharide (LPS) of serotype 026:B6--on the respiratory splash (RS) of neutrophils and monocytes in peripheral blood of patients with Familial Mediterranean Fever (FMF) was studied. It is shown that FMF patients have a periodic increase (during an attack) and a decrease (in the period of remission) in endotoxin-induced RS of neutrophils and monocytes. LPS stimulates chemotoxis-induced RS of neutrophils and monocytes in patients both in the period of remission and during the attack equally effectively. Iodine-lithium-alpha-dextrin and sodium thiosulfate have a marked anti-endotoxic effect which manifests with quick neutralization of endotoxin activity on RS of monocytes and neutrophils in FMF patients both during the attack and remission.
Assuntos
Dextrinas/farmacologia , Febre Familiar do Mediterrâneo/imunologia , Granulócitos/efeitos dos fármacos , Lipopolissacarídeos/antagonistas & inibidores , Explosão Respiratória/efeitos dos fármacos , Tiossulfatos/farmacologia , Adolescente , Adulto , Escherichia coli/imunologia , Feminino , Humanos , Iodo , Lipopolissacarídeos/imunologia , Lítio , Masculino , Monócitos/efeitos dos fármacosRESUMO
We investigated spontaneous, chemotaxis-, phagocytosis- and proteinkinase C-dependent respiratory burst of neutrophils and monocytes in the whole blood of patients with familial Mediterranean fever (FMF). We also analysed transient activation of neutrophils and monocytes on the level of a single cell using flow cytofluorimetry. It is shown that compared to healthy donors, the respiratory burst of monocytes and neutrophils in the patients is characterized by an increase in both spontaneous and inducible production of free radicals. In FMF patients probability of transient activation of chemotaxis- and phagocytosis-dependent respiratory burst is higher. This has an important influence rather on production of free radical by activated cells than on their number.
Assuntos
Febre Familiar do Mediterrâneo/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Explosão Respiratória , Adolescente , Adulto , Radicais Livres , Humanos , Ativação de Neutrófilo , FagocitoseRESUMO
The influence of colchicine on the spontaneous and chemotaxis-, protein kinase C-, and phagocytosis-induced respiratory burst of neutrophils and monocytes in the peripheral blood of patients with familial Mediterranean fever (FMF) has been studied. The transient activation of neutrophils and monocytes on the level of a single cell has been monitored by means of flow cytofluorimetry. It is shown that colchicine blocks the induction of chemotaxis-, phagocytosis-, and proteinkinase C-dependent respiratory burst in vitro, as well as the increased pro-oxidant transient activation of neutrophils and monocytes of FMF patients, both in the period of remission and during the FMF attack. Colchicine stimulates the intensity of the spontaneous respiratory burst of neutrophils and monocytes in patients in the course of remission and during the FMF attack. At the same time, the drug effectively suppresses the periodicity of the multidirectional transient activation of the respiratory burst of effector cells during FMF.
Assuntos
Colchicina/farmacologia , Febre Familiar do Mediterrâneo/metabolismo , Supressores da Gota/farmacologia , Granulócitos/metabolismo , Monócitos/metabolismo , Explosão Respiratória/efeitos dos fármacos , Adolescente , Adulto , Células Cultivadas , Quimiotaxia/efeitos dos fármacos , Febre Familiar do Mediterrâneo/patologia , Feminino , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Ativação de Neutrófilo/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Proteína Quinase C/metabolismoRESUMO
Disturbances in the regulation of phagocytic activity of neutrophils and monocytes (PANM) in whole peripheral blood of patients with familial Mediterranean Fever (FMF), which had not received treatment with colchicines, were determined by quantitative flow cytofluorimetry. The effect of iodine-lithium-alpha-dextrin (armenicum) and colchicine on the PANM in the blood of FMF patients was studied in vitro. The intensity of phagocytosis in populations of neutrophils and monocytes in FMF patients (n = 6) during the remission period is higher than that during the FMF attack (n = 6) and higher than in healthy donors (n = 9). The PANM in patients during the FMF attack is higher compared to that in healthy donors. Iodine-lithium-alpha-dextrin (armenicum) and colchicine inhibited the phagocytosis of effector cells in FMF patients in a dose-dependent and time-dependent manner. It was shown that the suppressive effect of the drugs increased with decreasing bacteria/effector cells ratio.
Assuntos
Colchicina/farmacologia , Febre Familiar do Mediterrâneo/imunologia , Granulócitos/efeitos dos fármacos , Iodo/uso terapêutico , Lítio/uso terapêutico , Monócitos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Adolescente , Adulto , Dextrinas , Portadores de Fármacos , Feminino , Granulócitos/imunologia , Humanos , Masculino , Monócitos/imunologiaRESUMO
AIM: To study spontaneous chemotaxis-, phagocytosis-, and proteinkinase C-mediated respiratory splash (RS) of neutrophils and monocytes in colchicin-untreated patients with familial Mediterranean fever (FMF). MATERIAL AND METHODS: Of 17 FMF patients, 8 ones were examined during the attack, 9 patients--in fever-free period. Spontaneous and induced RS of peripheral blood neutrophils and monocytes was investigated with quantitative flow-cytofluorimetric method. RESULTS: Compared to healthy donors, RS is characterized with activation of both spontaneous and induced production of free radicals. The activity and intensity of the RS in FMF was low in the attack vs in the attack-free period but monocytes population has a stable high activity of the RS. CONCLUSION: Activation of neutrophilic RS in FMF patients is characterized by periodicity the direction of which is opposite to induced monocyte activation in the attack and in attack-free interval.
Assuntos
Febre Familiar do Mediterrâneo/sangue , Monócitos/metabolismo , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/sangue , Explosão Respiratória/fisiologia , Adolescente , Adulto , Biomarcadores/sangue , Citometria de Fluxo , Humanos , Índice de Gravidade de DoençaRESUMO
The binding of adriamycin and ethidium bromide coupled to sepharose beads with intracellular and serum immunoglobulins is detected. These drugs do not bind with Fab and Fc fragments of immunoglobulin. The binding of ethidium bromide to immunoglobulins is competitive. Possible adaptive features of this phenomenon are discussed.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Doxorrubicina/farmacocinética , Etídio/farmacocinética , Imunoglobulinas/efeitos dos fármacos , Marcadores de Afinidade , Animais , Linfócitos B/imunologia , Ligação Competitiva/efeitos dos fármacos , Linhagem Celular , Doxorrubicina/análise , Interações Medicamentosas , Resistência a Medicamentos , Eletroforese em Gel de Poliacrilamida , Etídio/análise , Etídio/antagonistas & inibidores , Humanos , Hibridomas/imunologia , Hibridomas/metabolismo , Immunoblotting , Imunoglobulinas/análise , Imunoglobulinas/metabolismo , Camundongos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/metabolismo , Ligação Proteica/efeitos dos fármacos , Células Tumorais Cultivadas/imunologia , Células Tumorais Cultivadas/metabolismoRESUMO
A dose-dependent stimulation of immunoglobulin synthesis by Spebr-5 cells in the presence of adriamycin is shown. This effect is significantly blocked in the presence of iron-chelating agent 2,2-bipyridine. Moreover, low doses of H2O2 and heat shock also caused enhancement of immunoglobulin synthesis. These data suggest the involvement of free radical processes in the adriamycin induced stimulation of immunoglobulin synthesis.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Doxorrubicina/farmacologia , Imunoglobulinas/efeitos dos fármacos , Mieloma Múltiplo/metabolismo , 2,2'-Dipiridil/farmacologia , Animais , Linhagem Celular , Cisteína/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Resistência a Medicamentos , Etídio/antagonistas & inibidores , Glutationa/farmacologia , Imunoglobulinas/biossíntese , Camundongos , Mieloma Múltiplo/imunologia , Estimulação Química , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismoRESUMO
Effects of cytotoxic drugs, doxorubicin (adriamycin) and ethidium bromide, on immunoglobulin production have been studied in B-cell hybridomas, myelomas and human lymphocytes. Doxorubicin, and in a lesser extent ethidium bromide, are shown to enhance immunoglobulin production both in drug-resistant and drug-sensitive cell lines. Enhancement of immunoglobulin production is accompanied with that of the number of antibody forming cells and with immunoglobulin synthesis in these cells.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Doxorrubicina/toxicidade , Etídio/toxicidade , Hibridomas/efeitos dos fármacos , Imunoglobulinas/efeitos dos fármacos , Mieloma Múltiplo/imunologia , Adaptação Fisiológica/imunologia , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Células Produtoras de Anticorpos/imunologia , Linfócitos B/imunologia , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/imunologia , Humanos , Hibridomas/imunologia , Imunoglobulinas/análise , Imunoglobulinas/biossíntese , Camundongos , Estimulação Química , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/imunologiaRESUMO
The influence of cytotoxic agents adriamycine (AD) and ethydium bromide (EB) on Ca(2+)-dependent K+ channels of erythrocytes was investigated. The incubation of erythrocytes with agliconic part of AD (without aminosugar residue) increased Ca(2+)-dependent K+ efflux induced by low concentration of propranolol, while EB suppressed the activating effect of propranolol. EB, verapamil and triphluoroperazine inhibited Ca(2+)-dependent K+ efflux induced by high doses of propranolol. The incubation of erythrocytes with AD took off the inhibitory action of EB and verapamil but did not influence the blocking effect of triphluoroperazine. Both AD and EB did not influence Ca(2+)-dependent K+ channels induced by Ca(2+)-ionophore A23187, and Pb(2+)-dependent K+ efflux from erythrocytes. It is suggested that opposite effects of AD and EB on Ca(2+)-dependent K+ channels are due to activation by AD and inhibition by EB of system of Ca2+ transport into cells, but not on their action directly on K+ channel.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Cálcio/sangue , Doxorrubicina/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Etídio/farmacologia , Canais de Potássio/efeitos dos fármacos , Calcimicina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Técnicas In Vitro , Ionóforos/farmacologia , Oxirredução/efeitos dos fármacos , Potássio/sangue , Propranolol/farmacologia , Trifluoperazina/farmacologia , Verapamil/farmacologiaRESUMO
34 patients with nasal polyps (NP) and 12 normal individuals were studied immunologically to investigate association of nasal polyp formation with disorders of general and local immunity. In NP patients there were decreased preoperative and early postoperative levels of peripheral blood T- and B-lymphocytes, functional activity of lymphocytes and neutrophils. In contrast to normal individuals, nasal secretion of NP patients contained degenerative epithelial cells and neutrophils, activated lymphocytes, monocytes and eosinophils. Nasal polyp tissues obtained after polypectomy contained more B-lymphocytes than T-lymphocytes. Lymphocytes and neutrophils in nasal polyps had elevated functional activity in tissue culture. We conclude that local hyperactivation of T- and B-lymphocytes as well as neutrophils contribute much to nasal polyp formation.
Assuntos
Sinusite Etmoidal/complicações , Sinusite Etmoidal/imunologia , Pólipos Nasais/complicações , Pólipos Nasais/imunologia , Adulto , Antígenos CD/imunologia , Linfócitos B/imunologia , Sinusite Etmoidal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/cirurgia , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Linfócitos T/imunologiaRESUMO
Target cells, K562 strain and its sublines characterized by multiple drug resistance (MDR) do not differ in their susceptibility to human natural killer cells (NK) but MDR cells are more susceptible to cytotoxic action of lymphokine-activated cells (LAC) and to NK cells in the presence of a selective agent adriamycin. Target cells death is characterized by fragmentation of nuclear DNA. It has been established that K562 thermotolerant subclone is more resistant to NK and LAC than other clones. Heat shock protein synthesis may have a protective impact in target cells death during interaction with NK and LAC cells.