Biomedical subjects

G Eissner

Publications and source records attributed to G Eissner.

At least 19 recordsLinked to original sources

PubMed1995

Critical involvement of transmembrane tumor necrosis factor-alpha in endothelial programmed cell death mediated by ionizing radiation and bacterial endotoxin.

In this report, we show that ionizing radiation (IR) at a clinically relevant dose (4 Gy) causes apoptosis in macrovascular and microvascular human endothelial cells. Treatment of irradiated cells with a low dose of bacterial endotoxin (LPS), similar to the levels observed in serum during endotoxemia, enhanced the rate of apoptosis, although LPS alone was unable to induce programmed cell death. The cytokine and endotoxin antagonist interleukin-10 (IL-10) reduced the rate of LPS + IR-induced apoptosis to levels obtained with irradiation alone. Using neutralizing antibodies against tumor necrosis factor-alpha (TNF), we could show crucial involvement of TNF in the LPS-mediated enhancement of IR-induced apoptosis, but not in the IR-induced apoptosis per se. However, further analysis strongly suggested the transmembrane form of TNF (mTNF), but not soluble TNF, to be accountable for the LPS-mediated cytotoxic effects. Studies with anatagonistic receptor specific antibodies clearly showed that TNF receptor type I (TR60) is essential and sufficient to elicit this effect. These findings are of potential clinical importance because they may disclose a relevant mechanism that leads to endothelial damage after radiotherapy or total body irradiation used for conditioning in bone marrow transplantation and that may thus contribute to transplant related complications, especially in association with endotoxemia or related inflammatory states.

Animals↗

PubMed1995

CD3- large granular lymphocytes recognize a heat-inducible immunogenic determinant associated with the 72-kD heat shock protein on human sarcoma cells.

Traditionally, heat shock proteins (HSPs) are believed to be located intracellularly, where they perform a variety of chaperoning functions. Recently, evidence has accumulated that some tumor cells express HSPs on the cell surface. The present study confirms this finding and correlates HSP72 cell surface expression, induced by nonlethal heat shock, with an increased sensitivity to interleukin-2-stimulated CD3-natural killer (NK) cells. After nonlethal heat shock, a monoclonal antibody directed against the major heat-inducible 72-kD HSP (HSP72) stains the cell surface of sarcoma cells (ie, Ewing's sarcoma cells or osteosarcoma cells) but not that of normal cells (ie, peripheral blood lymphocytes, fibroblasts, phytohemagglutin-stimulated blasts, B-lymphoblastoid cell lines) or of mammary carcinoma cell line MX-1 carcinoma cells. In this study, we show for the first time a correlation of HSP72 cell surface expression with an increased susceptibility to lysis by NK effector cells. This finding is supported by the following points: (1) HLA-disparate effector cells show similar, elevated lysis of HSP72+ heat-treated sarcoma cells; (2) CD(3-) NK cells, but not CD3+ cytotoxic T lymphocytes, are responsible for the recognition of heat-shocked sarcoma cells; (3) by antibody-blocking studies, an immunogenic HSP72 determinant, which is expressed selectively on the cell surface of heat-treated sarcoma cells could be correlated with NK recognition; (4) the reported phenomenon is independent of a heat-induced, transient downregulation of major histocompatibility complex (MHC) class-I expression; and (5) blocking of MHC class-I-restricted recognition, using either MHC class-I-specific monoclonal antibody W6/32 on the target cells or alpha/beta T-cell receptor monoclonal antibody WT31 on effector cells, also has no inhibitory effect on the lysis of HSP72+ tumor cells. Finally, our in vitro data might have further clinical implications with respect to HSP72 as a stress-inducible, sarcoma-specific NK recognition structure.

Antibodies, Monoclonal↗

PubMed1994

Ionizing radiation induces human intercellular adhesion molecule-1 in vitro.

Intercellular adhesion molecule-1 (ICAM-1) plays a central role in various inflammatory reactions and its expression is readily induced by inflammatory stimuli such as cytokines or ultraviolet irradiation. We have investigated the effect of ionizing radiation (IR) on human ICAM-1 expression in human cell lines and skin cultures. ICAM-1 mRNA levels in HL60, HaCaT, and HeLa cells were elevated at 3-6 h after irradiation and increased with doses from 10-40 Gy. The rapid induction of ICAM-1 occurred at the level of transcription, was independent of de novo protein synthesis, and did not involve autocrine stimuli including tumor necrosis factor-alpha and interleukin-1. IR also induced ICAM-1 cell surface expression within 24 h. Immunohistologic analysis of cultured human split skin revealed ICAM-1 upregulation on epidermal keratinocytes and dermal microvascular endothelial cells 24 h after exposure to 6 Gy. In conclusion, we propose ICAM-1 as an important radiation-induced enhancer of immunologic cell adhesion, which contributes to inflammatory reactions after local and total body irradiation.

Antibodies↗

PubMed1994

Differential role of protein kinase C in cytokine induced lymphocyte-endothelium interaction in vitro.

In the present study we investigated the influence of the PKC-inhibitor GF109203X on cytokine- and endotoxin-induced expression of intercellular adhesion molecule 1 (ICAM-1) and on the adhesion of lymphocytes to cytokine-activated endothelial cells. We found that tumour necrosis factor alpha (TNF-alpha)- and lipopolysaccharide (LPS)-induced ICAM-1 expression on a human endothelium-derived cell line (EA.hy926) were unaffected by the PKC-inhibitor and thus appeared to be independent of PKC activation. In contrast, GF109203X significantly reduced ICAM-1 expression induced by interferon-gamma (IFN-gamma) and interleukin-1 (IL-1). The functional relevance of these findings was evaluated in an adhesion assay using human umbilical vein endothelial cells (HUVEC) and peripheral blood mononuclear cells (PBMC). In fact, the IFN-gamma- and IL-1-induced adhesion of PBMC to cytokine treated HUVEC could be down-regulated by the PKC-inhibitor, whereas TNF alpha- and LPS-mediated adhesion was not affected. Additionally, the IL-1-driven ICAM-1 expression on HUVEC as well as the IL-1 induced adhesion of PBMC to HUVEC was found to be TNF-dependent, as both effects could be inhibited by an anti-TNF-alpha monoclonal antibody (MoAb) (MAK195). Based on these data on differential regulation of cytokine-induced lymphocyte-endothelium interactions our study supports the use of PKC-inhibitors as additive modulators in cytokine related pathophysiological conditions.

Cell Adhesion↗

PubMed1992