Klaus G. Stunkel

Administration of silica or monoclonal antibody to Thy-1 prevents low-dose streptozotocin-induced diabetes in mice

Multiple injections of low doses of streptozotocin induce an experimental diabetes in mice. We have analyzed in two inbred strains whether the development of hyperglycaemia can be influenced by administration of macrophage-toxic silica particles or by a monoclonal antibody to Thy-1.2. Mice received streptozotocin (30 or 40 mg/kg) on five consecutive days (day 0-day 4) and in addition either silica particles (starting at day 0) or anti-Thy-1.2 (starting at day -2 or -3). In both strains mice receiving streptozotocin alone became hyperglycaemic within two weeks. Additional treatment with silica almost fully prevented diabetes development. Anti-Thy-1.2 administration was similarly effective in C57B1/Ks and partially protective in C57BL/6 mice. Histological analysis of pancreatic islets showed that a large fraction of beta cells had been spared from destruction by this treatment. The data indicate a role for both macrophages and Thy-1 positive cells in the pathogenesis of low-dose streptozotocin-induced diabetes.

Ciprofloxacin enhances T cell function by modulating interleukin activities

Ciprofloxacin (CIP) is a quinolone carboxylic acid derivative with a broad spectrum of antibacterial activity. CIP (0.1–30 μg/ml) enhanced DNA synthesis of mouse spleen cells and human peripheral blood lymphocytes (PBL) that had been activated with T cell mitogens or with alloantigens. In addition, CIP increased the amount of IL‐2 found in the supernatants of phytohaemagglutinin (PHA)‐stimulated human PBL. The presence of CIP in the medium (0.3–10 μg/ml) increased the levels of IL‐1 found in the culture supernatants of adherence‐enriched mouse macrophages, human monocyte/macrophages and a human monocytic cell line stimulated with lipopolysaccharide. In contrast there was no effect of CIP on the release of IL‐1 by freshly isolated human monocytes or by cells of the keratinocyte line, A431. CIP alone had no influence on the basal release of IL‐2 by NOB‐1 cells, a Tcell line that responds to IL‐1 with an increase in IL‐2 synthesis, but, in combination with recombinant IL‐1, CIP significantly enhanced the release of IL‐2 by these cells. The results of this study suggest that CIP modulates the immune response at two levels—the production of IL‐2 by activated T cells and the production of IL‐1 by activated monocyte/macrophages. However. CIP did not affect the primary antibody response in vitro or in vivo against sheep erythrocytes and ovalbumin respectively. Thus the enhancing action of ciprofloxacin on the immune system appears to be restricted to T cell function and macrophage/T cell interactions.

A method for the quantitation of interleukin-2 activity

A bioassay for the determination of interleukin-2 activity is described. We have compared the traditional method of data processing, which involves probit analysis and curve fitting, with a simpler method based on the so-called AUC (area under the curve). The latter method is readily applicable to spreadsheet software and can handle large amounts of data.

Linkage between monokine production and regulation of the negative surface charge density of human monocytes

The regulation of the negative surface charge density of human monocytes was investigated with the help of the synthetic glycolipid analogue BAY R 1005. This compound is incorporated into the outer membrane of isolated monocytes during 24 hours of incubation. After this time the electrophoretic mobility (EM) of monocytes is unchanged at 0.95 x 10(-4) (cm2 V-1 s-1) and remains unchanged even under conditions where non-treated monocytes increase their EM up to 1.1 x 10(-4) (cm2 V-1 s-1). In addition BAY R 1005 stops differentiation of monocytes to macrophages, it triggers monokine production and abolishes monocyte suppressor activity and spreading capability. The results show that BAY R 1005 affects intracellular features. In connection with earlier investigations of the regulation of the negative surface charge density of human monocytes (1,2) the study suggests that monokine production and maintenance of the EM of monocytes are linked.

Cutaneous infiltrates of histiocytosis X contain plasminogen activator-bearing epidermotropic dendritic cells different from Langerhans cells.

SummaryPlasminogen activators (PA) play an important role in cell migration and tissue degradation. Considering the strong epidermotropism of atypical mononuclear cells in histiocytosis X (HX) skin infiltrates leading to intraepidermal abscess formation, it was the purpose of this study to look for tissue-type PA (t-PA) and/or urokinase-type PA (u-PA) on HX cells.Four monoclonal antibodies against PA were used, employing the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique on cryostat sections from four patients with HX. Twenty percent to 40% of infiltrating cells in the epidermis expressed the t-PA antigen. t-PA+ cells were present in the follicular centers of human tonsil, absent in normal epidermis and scanty in cutaneous infiltrates from mycosis fungoides and lupus erythematosus. Double labeling with anti-PA and T6 (CD1) or S100 protein revealed some of the HX cells to express both antigens (t-PA+ CD1+ or t-PA+ S100+).We conclude that cutaneous infiltrates of HX contain PA+ dendritic cells which are different from normal Langerhans cells and which may be responsible for the strong epidermal alterations in HX.