摘要:

AbstractAdenosine reportedly mediates myocardial and skeletal blood flow, bronchoconstriction, and cellular production of toxic oxygen radicals. Cellular effects of adenosine can be antagonized by the methylxanthines, which are widely used in the clinical treatment of obstructive airway diseases. Methylxanthine compounds such as aminophyl-line and theophylline inhibit the cyclic nucleotide phosphodiesterase of smooth muscle, reversing pathogenic states of bronchoconstr ict ion. Recent techniques in -flow cytometry allow examination of individual cells -for the electrophysiological and metabolic cellular side effects of methylxanthine therapy. We report that the flow cytometric examination of isolated canine peripheral neutrophils, in the presence of therapeutic concentrations of aminophylline resulted in small but significant membrane depolarization and almost fivefold increases in baseline cytosolic H202 levels. If aminophylline is capable of directin vitroactivation of isolated canine neutrophils it may have the capacity to potentiate neutrophil activationin vivo: indirectly by competing with circulating modifiers, such as adenosine, for cell surface receptor sites and directly by the induction of toxic oxygen radicals as demonstrated here. H2O2 induction by aminophyl-line and other xanthine derivatives may become clinically important in instances of vascular occlusion, stasis, or instances of reperfusion where neutrophils may become activated. In an activated state, neutrophils could contribute to pathogenecity and tissue damage by indiscrimin-antly releasing oxygen-reactive species.

ISSN:0892-3973    

DOI:10.3109/08923978909005362

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractPotassium channel activity has been implicated in the lytic function of cloned murine effector T lymphocytes (5) and human NK cells (12) as well as in the initiation of the injury process in tumor cells (23). In the present studies, the effects of various K+channel blockers on the cytolytic function ofin vivoderived alloimmune lymphocytes towards P815 tumor cells were evaluated. The classical K+channel blocker 4-aminopyridine (4-AP), the naturally occurring monoamine serotonin (5-hydroxytryptamine, 5-HT) and its agonist, quipazine, as well as the Ca++dependent K+channel blocker quinidine were chosen for investigation based on their known ion channel gating properties. These agents, when present in the assay medium, inhibited in a dose dependent manner the lysis of P815 tumor cells as measured by specific51Cr release. Preincubation of effector lymphocytes with the various K+channel blockers resulted in greater inhibition of lysis than did the preincubation of target cells. The 5-HT agonist quipazine was of particular interest in that it inhibited the lytic process with equal effectiveness when continuously present in the assay medium or when the effector cells alone were preincubated. Quinidine was used to investigate whether Ca++dependent K+channels were the predominant ion channel involved in the lytic process. When present during the lytic assay, quinidine was similar to quipazine in terms of their dose range at which they inhibited the lytic process. These results indicate that 5-HT sensitive Ca++dependent K+channels are likely to be involved in the delivery of lytic signal (s) by immune effector lymphocytes and suggests that neuroenocrine products may modulate the functional activity ofin vivoderived lymphocytes.

ISSN:0892-3973    

DOI:10.3109/08923978909005363

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractTreatment of mice with rifampin (Ri, 100-200 mg/kg) affected the course of contact sensitivity (CS) reactions to oxazolone. The effects which were seen as either partial inhibition or enhancement of the response, under one set of conditions, could be abrogated or even reversed if conditions of either induction, elicitation and time of measuring reactions were altered. In addition, amount of Ri used for treatment and time of treatment in relation to the induction of CS reactions also influenced the effects observed.

ISSN:0892-3973    

DOI:10.3109/08923978909005364

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractOffspring of mice treated with cyclophosphamide (Cy; 1, 2.5 or 5 mg/kg) during pregnancy (6-18 days of gestation) and tested for immunocompetence from 5 to 10 weeks of age were found to have defective reticuloendothelial clearance. The main effects were: a) increased elimination half time (T 1/2) of51Cr-labeled SRBC from circulation, b) decreased liver uptake of51Cr and c) impaired ability of the spleen, mostly affecting the female pups, to compensate for decreased liver uptake. The highest dose group suffered the most pronounced effects. This group was also found to have increased IgG immunoglobulin levels at 7 weeks of age. IgG antibody production in response to specific antigenic stimulation and delayed hypersensitivity reactions to oxazolone did not appear to be affected by Cy treatment.

ISSN:0892-3973    

DOI:10.3109/08923978909005365

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractFisher rats were treated for 28 or 60 days to multiple exposures to the smoke of marijuana or marijuana placebo cigarettes. Primary, secondary and in some instances tertiary tumor implants were performed. Murine sarcoma 180 tumor cells (7.5×107) were implanted subcutaneously on day 1, 14 and 28 following initiation of smoke exposure (28 day studies) or on day 1, 14 after cessation of smoke exposure (60 day studies). Tumor areas were measured on alternate days beginning on the second or third day after implantation for 13 or 14 days. Exposure to both marijuana and placebo smoke for 28 days (6, 9 and 18 cigarettes per day) resulted in suppressed growth of secondary and tertiary implants. Administration of△9tetrahydrocannabinol (50 mg/kg, i.p., 20 days) failed to suppress the growth of primary and secondary tumors. This suggests that noncannabinoid constituents of the smoke may contribute to the suppression of tumor growth. Exposure of rats to 9, but not 4 or 6, marijuana or placebo cigarettes per day for 60 days suppressed the growth of primary but not secondary tumors. Thus, the effects of smoke exposure appear to be lost by two weeks after cessation of treatment. The possible existence of a non-cannabinoid immunostimulant in the smoke is discussed.

ISSN:0892-3973    

DOI:10.3109/08923978909005366

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractThe in vitro effect of IFN-a on lymphocyte transformation and specific immune response against Brucella antigens was studied in 33 patients with chronic brucellosis and 10 normal controls. The following immunologic in Aditro tests were applied: PHA activated lymphocyte transformation test using Bromodeo-xyuridine and a monoclonal antibody in the presence and abscence of 50 and 100 IU IFN Alpha-2b and leukocyte migration inhibition test against Brucella antigens in the presence and abscence of 100 and 500 IU of IFN Alpha-2b. Patients were further divided to 2 subgroups according to a positive or negative migration inhibition test.Our results showed that T lymphocyte transformation was similar in patients and controls and that the addition of 50 IU IFN resulted in a significant increase of transforming cells whereas in the concentration of 100 IU IFN only anergic patients and controls responded positively. IFN also resulted in a significant leukocyte migration inhibition only in anergic patients and controls. These findings suggest that the chronic infection is not due to a generalized cellular immunodeficiency state and that IFN Alpha-2b might be a promising therapeutic approach in anergic patients.

ISSN:0892-3973    

DOI:10.3109/08923978909005367

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractThe augmentation of resistance against Listeria monocytogenes after an intraperitoneal (ip) administration of shosaiko-to in mice was shown to depend on the time interval between the treatment and the infection. A maximal effect was expressed in mice treated 4 days before ip infection. The time dependent resistance correlated to the accumulation of macrophages in the peritoneal cavity just before the infection, but not to bactericidal activity as judged by the fact that peritoneal macrophages from untreated mice and those from mice treated with shosaiko-to 4 days before showed a high bactericidal activity of the same degree. Resistance to the infection in untreated mice may be attributable to newly accumulating macrophages with a low level of bactericidal activity, but not to resident macrophages with a high level of the activity. After intravenous infection, on the other hand, a maximal effect was expressed in mice treated with shosaiko-to 2 days before. The resistance correlated to accumulation of macrophages and bactericidal activity in the spleen just before the infection. Participation of cytokines in an augmenting effect of shosaiko-to on protection against the infection was examined. Shosaiko-to induced a transient elevation of serum CSF activity that was maximal at 3 hours after the administration in uninfected mice, though it did not augment the CSF activity induced by the infection. The elevation of CSF activity may induce accumulation of macrophages with a high level of bactericidal activity in the spleen 2 days after administration of shosaiko-to and then in the peritoneal cavity 4 days after administration. IFN-γand TNF-αdid not participate in the effect because administration of anti-IFN-γor anti-TNF-αjust before administration of shosaiko-to or just before infection did not abrogate the inhibitory effect of shosaiko-to on the bacterial growth in the early stage of infection. Shosaiko-to also induced an increase of CFUm number in the spleen. The effect may contribute to the augmentation of resistance in the late stage of infection by differentiating to mature macrophages.

ISSN:0892-3973    

DOI:10.3109/08923978909005368

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractThe inactivated streptococcal preparation OK432 activates the cytotoxic function of natural killer (NK) cells. Moreover, it induces cytotoxic activity against freshly isolated tumor cells. The present study was aimed at assessing whether OK432-activated effector cells expressed cytotoxicity against tumor cells pleiotropically resistant to cancer chemotherapy agents. OK432-treated lymphoid cells killed the multidrug resistant (MDR) LOVO DX line as efficiently as drug sensitive parental LOVO N carcinoma line. Effector cells involved in killing MDR cells were low density large granular lymphocytes with NK functions. Activation of effector cells has the potential to complement conventional cytoreductive therapy by eliminating residual tumor cells surviving and resistant to chemotherapy.

ISSN:0892-3973    

DOI:10.3109/08923978909005369

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractCorticosteroids and anti-thymocyte globulin (ATG) have been extensively used in the treatment of autoimmune diseases, aplastic anemia and organ graft rejection; nonetheless, the precise mechanisms of action of these agents are unknown. Studies of their long term immunoregulatory effects, particularly in humans, have been limited. We examined the long terra effects of therapy with ATG given for 2-4 weeks and prednisone for 2 months in 4 patients with newly diagnosed insulin dependent diabetes (IDD). Three matched newly-diagnosed untreated IDD patients and 17 healthy volunteers served as controls. No differences in total lymphocyte count, percentage of B cells, percentage of total T cells (CD3), helper-inducer T cells (CD4) or cytotoxic-suppressor cells (CD8), lymphocyte blastogenesis assays, or pokeweed mitogen-induced IgG secretion in T + B cell co-cultures were detected before therapy. A transient lymphopenia following ATG administration was the only immunological defect found in the first month of therapy. At 2 months, however, patients treated with ATG and prednisone had diminished immunoregulatory T cell function demonstrated by production of only 28±3% IgG expected in T + B co-culture, compared to 205±35% for untreated IDD patients and 107±13% for normals (p<0.01). This diminished IgG production resulted from excessive suppressor function, since co-cultures of T cells from treated patients with T and B cells from normal volunteers suppressed the latter's IgG production by 76±9%. This enhanced suppressor activity persisted for 3-6 months following therapy. Other immunological functions were not statistically different from those present at the inception of the study. Thus, treatment with corticosteroids and ATG produces long-term enhanced suppressor activity, a finding which suggests that treatment with combination ATG and Prednisone is a rational form of immunomodulation in conditions associated with decreased suppressor function.

ISSN:0892-3973    

DOI:10.3109/08923978909005370

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

AbstractLuminol-enhanced chemiluminescence assay was used to detect the surface expression and the consequent activation of receptors (FcRI and FcRII) of murine macrophages (Møs). When murine IgG2awas used for the specific detection of FcRI and IgG2bfor FcRII, a newly established procedure enabled us to detect the activation of each receptor with as few as 3×105Møs. Briefly, TNP-SRBC coated with monoclonal IgG2aor IgG2bantibodies directed to TNP (sensitized SRBC) were used as reagent, in the presence of 1×10−5M luminol, and the emission was measured with a liquid scintillation counter.When results obtained by chemiluminescence counting were compared to the results obtained by the rosette formation by adding the same SRBC reagent to peritoneal Møs obtained after ip injection of Listeria, fortified chemiluminescence counting allowed us to obtain a more definite answer about the activation of each receptor.Under the conditions established, the specific activation of FcRI was obtained by the addition of rIFNαrA/D to the resident Møs in vitro and the specific activation of spleen MøFcRII by iv injection of IAP (Immunosuppresive acidic protein) into mice. These two results supported the independence of the two receptors detected by the assay.

ISSN:0892-3973    

DOI:10.3109/08923978909005371

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor