Journal of immunopharmacology最新文献

The percentage T-lymphocyte subpopulations were determined with the aid of radioactively-labelled monoclonal antibodies to the antigens of total T-lymphocytes and to suppressor T-lymphocyte surface antigens and the responsiveness of the lymphocytes in the presence of ConA and PHA was investigated in groups of 8 subjects aged either between 20 and 30 years or over 75 years. It was found that there was no difference with respect to the response of the lymphocytes to the plant mitogens ConA and PHA. The percentage of suppressor T-lymphocytes, on the other hand, was significantly reduced in the older subjects, whilst the percentage of total T-lymphocytes did not differ significantly from the percentage in younger subjects. These results are discussed in connection with published data.

We examined the effects of two prostaglandin synthetase inhibitors, aspirin and oxaprozin, on the development of lupus-like disease in MRL/1 mice. Daily oral administration of 100 mg/kg of these compounds over a period of 3 months significantly reduced thymic lymphoid hyperplasia. In addition, aspirin but not oxaprozin significantly lowered total lymphocyte counts in the peripheral blood. Other drug-related changes, including reduced hyperplasia in the spleen and lymph nodes and an improvement in kidney vasculitis by aspirin, did not reach statistical significance. Neither aspirin nor oxaprozin influenced the circulating levels of anti-ds DNA antibodies or the severity of kidney glomerulonephritis. While the overall effects of these cyclooxygenase inhibitors were not dramatic, the results do indicate that further studies are warranted to determine the precise therapeutic role, if any, for PG-synthetase inhibitors in lupus-like disease.

Cytochalasin-E (CE) has specific properties that distinguishes it from other cytochalasin congeners. We have taken advantage of these in investigating the mechanisms operative in the effects of cytochalasins on lymphocyte proliferative responses to phytomitogens. Like the other cytochalasins, CE inhibits these responses only when present during the early phases of exposure of lymphocytes to mitogens, but not when added later on. The effects of CE are irreversible since prior incubation of lymphocyte in CE renders them incapable of response. Unlike the effects of cytochalasin A, the only other irreversibly active congener, lymphocytes preincubated in CE completely recover the ability to respond if they are cultured in cytochalasin-free medium for 48 hours. Unlike cytochalasins A and B, cytochalasin-E does not inhibit glucose transport into lymphocytes and all. We have shown that human lymphocytes bind cytochalasins at 3 distinct classes of sites named L, M, and H (J. Biol. Chem. 256:1290-1300, 1981). CE binds irreversibly to the L and H-sites on the short to medium term but does not bind to the glucose displaceable M-site at all. CE may have potential usefulness as affinity label towards isolation of specific binding sites since the chemical structure offers feasible approaches towards isotopic labelling.

The numbers of T lymphocytes, helper and suppressor T lymphocytes, were measured in peripheral blood of 10 patients, 13 patients with gastric cancer and 20 normal controls. T lymphocyte subpopulations were enumerated by the use of monoclonal antibodies OKT3 (pan-T lymphocytes), OKT4 (helper/inducer lymphocytes) and OKT8 (cytotoxic/suppressor lymphocytes) in an indirect immunofluorescence technique. Furthermore, the possible pharmacological modulation of 10(-4) histamine and 10(-4), 10(-6) M cimetidine of T lymphocyte subsets was investigated. Lymphocyte subpopulations were found to range in normal values in patients with ulcer and chronic gastritis. A marked decrease of OKT3 and OKT8 positive lymphocytes was noted in patients with gastric cancer, whereas OKT4 lymphocytes from the three groups of patients to histamine and cimetidine resulted in no significant changes of lymphocyte subsets.

Tricyclic antidepressant-induced perturbations of murine splenic lymphocyte membranes and cell surface concanavalin A receptor mobility have been investigated using the fluorescent probes diphenylhexatriene and fluorescein-conjugated concanavalin A. Results of these studies illustrate the possible relationship between tricyclic antidepressant-induced membrane perturbations and tricyclic antidepressant-induced suppression of the normal murine lymphocyte mitogen response. Tricyclic antidepressant effects on murine splenic lymphocyte membranes are dose-, time- and temperature- dependent. Murine lymphocyte concanavalin A cell surface receptor mobility is not apparently altered by the tricyclic antidepressants.

Collagen arthritis in rats has a well defined humoral and cellular immunologic response to type II collagen, the inciting antigen. Like other chronic models of inflammation, considerable variation exists in terms of severity and incidence. We have attempted to correlate the inflammatory response as measured by paw volume, with serum type II collagen antibody and skin delayed hypersensitivity (DH) to type II collagen. Surprisingly, the incidence and severity of collagen arthritis, induced in the presence of MDP to increase incidence of the disease, are neither correlated with type II collagen antibody nor DH to type II collagen. However, tarsometatarsal bone erosion is significantly correlated with paw edema. Further studies will be necessary to elucidate the role of both humoral and cellular immune responses in the development of type II collagen arthritis in the rat.

Perturbation of the neutrophil membrane by opsonized zymosan particles activates the cell's "respiratory burst." Associated with this activation process is the generation of highly reactive oxygen products, including superoxide, and the release of lysosomal enzymes. Membrane activation also stimulates arachidonic acid metabolism and the generation of a wide variety of products through both the lipoxygenase and cyclooxygenase pathways. In isolated human neutrophils, we have evaluated the effects inhibitors of cyclooxygenase and lipoxygenase upon opsonized zymosan stimulated chemiluminescence, superoxide generation, oxygen consumption, and beta-glucuronidase release. Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase enzyme, suppressed chemiluminescence, superoxide generation, oxygen consumption, and beta-glucuronidase release. Both indomethacin, a cyclooxygenase inhibitor, and 5,8,11,14 - eicosatetraynoic acid (ETYA) an inhibitor of both cyclooxygenase and lipoxygenase, inhibited all tested neutrophil functions. However, when compared to NDGA, indomethacin and ETYA were considerably less potent. Our observations suggest that the lipooxygenase derived metabolites play a predominant regulatory role in these neutrophil inflammatory functions.

Natural killer (NK) cell activity of mice given a single injection of manganese chloride (MnCl2) was significantly enhanced as measured in a 4-hr in vitro 51Cr release assay. Enhanced activity persisted for several days after injection. This cytotoxic activity was associated with nonadherent spleen cells and was completely eliminated by injecting MnCl2-treated mice with anti-asialo GM1 serum. Manganese-enhanced natural cytotoxicity was observed in several mouse strains with differing NK cell reactivity (CBA/J, C57BL/6, A/J, C3H/HeJ, and C57BL/6 beige mice) and with several tumor target cells with differing sensitivity to NK cytolysis (YAC-1, RBL-5, EL-4, and P815). The growth of B16-F10 melanoma lung tumors was inhibited in mice injected with MnCl2 one day before tumor challenge. Manganese chloride enhancement of NK cell activity appeared to be mediated by interferon (IFN). Low levels of IFN were detected in the serum of mice as early as 4 hr after MnCl2 injection. Rabbit anti-mouse IFN alpha, beta but not anti-mouse IFN gamma completely eliminated the MnCl2-enhanced NK cell activity in the spleens of mice. The observed enhancement of NK cell activity by MnCl2 is similar to that reported for more complex molecules that act by inducing IFN production.

The effects of subcutaneously or intraperitoneally administered dextran sulphate (DXS) (50 mg/Kg) on the subsequent 1 h localization of intravenously injected radiolabelled lymph node cells was investigated in complement deficient mice which lack C5. DXS proved to be equally as potent in depressing cell localization in deficient as compared to normal mice. These findings indicate that the terminal complement components are not essential for DXS activity.

The in vitro effect of levamisole on peripheral blood monocyte (P.B.M.) phagocytosis was studied in 32 patients with chronic brucellosis and 20 normal subjects. It was shown that levamisole enhances P.B.M. phagocytic capacity, not reaching however normal levels. A subgroup of 11 patients were treated with levamisole for 6 months and the drug effect on cellular and humoral immunity and monocyte phagocytosis was also studied. By the end of the 6 month treatment-study period, the following results were obtained: 1. six patients were symptom free while five had significantly improved. 2. T lymphocyte number and monocyte phagocytosis reached normal values. 3. Significant specific cellular immunity against both brucella antigens was noted. 4. B. lymphocytes showed no significant changes. 5. Antiglobulin titers varied. These findings suggest that the good therapeutical effect of levamisole in patients with chronic brucellosis could probably be a attributed to the enhancement of both T-cell function and monocyte phagocytosis.