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K G Stünkel

Publications and source records attributed to K G Stünkel.

10 recordsLinked to original sources
PubMed1992

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.

Cell Differentiation↗
PubMed1991

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 micrograms/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 micrograms/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 T cell 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.

Animals↗
PubMed1989

Biodistribution of anti-interleukin 2 receptor monoclonal antibodies correlates with their therapeutic efficacy following transplantation.

IL-2R-targeted therapy prevents graft rejection in various experimental models and in man. However, the principles of optimal mAb selection remain elusive, as their efficacy in vivo does not always correlate with their characteristics in vitro. ART-18 and OX-39, mouse IgG1 mAbs, define distinct epitopes on the p55 subunit of the rat IL-2R. Treatment of LEW hosts with ART-18 prolongs survival of LBN cardiac allografts up to a month; in contrast, OX-39 never affects acute (8-day) rejection. In this study, we evaluated the biodistribution of 125I-labeled ART-18 and OX-39 administered iv to untreated and heart-grafted rats. ART-18 was cleared from the circulation (half-life time ca. 29 hr) and accumulated in host lymph nodes and spleen to a greater extent than OX-39 (P less than 0.001). In contrast, OX-39 was retained in blood (half-life time ca. 66 hr) and was eventually sequestered in liver, lungs, and kidneys, a pattern comparable to an irrelevant IgG1 (MOPC-21). ART-18 but not OX-39 entered specifically acutely rejecting allografts (allograft:native heart activity ratio = 4.0 and 2.3, respectively, P less than 0.01). The distribution of ART-18 was IL-2R epitope but not mAb isotype specific as tissue accumulation of "hot" ART-18 was comparable in recipients conditioned with "cold" ART-18 of IgG1 or IgG2b isotype, but not in those treated with OX-39. Thus: (1) the biodistribution of anti-IL-2R mAbs is not random; the mAb "effective" in combating rejection (ART-18) penetrates preferentially host lymphoid tissues and the graft itself, whereas the biologically "ineffectual" mAb (OX-39) is retained in the circulation for prolonged periods; (ii) the epitope of IL-2R defined by the mAb is critical; a mAb may be "captured" by unrelated cells expressing a common epitope in vivo before reaching the related targets, and/or some epitopes may be more accessible than others for iv administered mAbs.

Animals↗
PubMed1989

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.

Animals↗
PubMed1988

Monitoring of interleukin-2 receptor (IL-2R) expression in vivo and studies on an IL-2R-directed immunosuppressive therapy of active and adoptive adjuvant-induced arthritis in rats.

Recent evidence indicates that adjuvant arthritis (AA) of rats induced by complete Freund's adjuvant (CFA) is an autoimmune disease that is mediated by T cells. This report describes the distribution of activated IL-2 receptor (IL-2R)-bearing cells in spleen, popliteal lymph nodes (PLN) and blood in AA rats and in naive healthy rats using the monoclonal antibody (mAb) ART-18. It was found that in the primary lymph nodes (injected side) two peaks of elevated numbers of IL-2R-positive cells (Day 9/10 with a 40-fold increase; Day 25 with a 75-80-fold increase) occur. The PLN of the non-injected site also show an increase (30-fold) in the number of IL-2R-positive cells on Day 25. This investigation also included the monitoring of soluble IL-2R in the serum of AA rats in comparison to control sera of non-induced rats. The incidence of free IL-2R in the serum of AA rats does not completely correlate with the pattern of the distribution of receptor-bearing cells in PLN; elevated levels of IL-2R were observed at Day 9 and subsequently declined to below control levels. On Day 25, there was no correlation between IL-2R+ cells and soluble IL-2R. ART-18 was not active in suppressing the development of AA, in contrast to the complete inhibition of the passively transferred AA.

Animals↗
PubMed1987

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

Plasminogen 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.

Aged↗
PubMed1987

Monoclonal antibodies detecting plasminogen activators on the membrane of leukemic lymphoid cells of T-cell origin.

The specificities of six monoclonal antibodies produced against plasminogen activator of the human Bowes melanoma cell line are described. They have been used to detect membrane-bound plasminogen activator on cultured human lymphoid cell lines and in neoplastic human lymphocytic and myeloid cells of leukemic patients. These studies indicate that only certain phenotypic subsets of the T-cell lineage derived from patients with chronic lymphocytic leukemia or with Szezary syndrome express plasminogen activator on their surface membrane.

Animals↗
PubMed1986

Activation of murine B lymphocytes by suramin.

Suramin stimulated DNA synthesis in spleen cell cultures of all inbred strains of mice tested, including, for example, CBA, DBA/2, C57BL/6, and the lipopolysaccharide (LPS)-nonresponsive strain C3H/HeJ. The cells responding to the drugs were removed by passage through nylon wool columns, but they were not eliminated by in vivo treatment of the mice with anti-Thy 1.2 antibody. Spleen cells of homozygous nude mice (C57BL/6 or BALB/c background) were as reactive as those of their heterozygous littermates. Collectively the data show that suramin is a B-cell mitogen in the mouse.

Animals↗
PubMedDate not supplied

Isolation of human B-cell subpopulations for pharmacological studies.

Three groups of human peripheral blood B-lymphocytes were separated from each other by countercurrent centrifugal elutriation and free-flow electrophoresis. They differed in their state of maturation and in their capability to produce antibodies in vitro. These B-cell subpopulations were used to study features of a drug such as BAY R 1005. BAY R 1005 is a synthetic glycolipid analogue (GLA), which is supposed to modulate antibody synthesis. Mature, immunoglobulin- (Ig-) secreting B-lymphocytes secreted equal quantities of antibodies in the presence and in the absence of the GLA. BAY R 1005 was found to be without mitogenic activity on resting B-cells and did not induce them to produce antibodies. However, it supported the antibody production of preactivated B-lymphocytes. The in vitro preactivated B-cells were affected via monocytes. Only in vivo preactivated B-lymphocytes increased their antibody production under the direct influence of BAY R 1005.

Antibody Formation↗