Les publications scientifiques de Eike G. Fischer

https://orcid.org/0000-0003-2033-2347

Cellule Pharmacologie / Immunologie :

• ß-Endorphin modulates immune functions - A review.
  Fischer EG, Falke NE (1984)
  Psychother.Psychosom. 42,1-4:195-204 [PMID] [DOI]
      [Abstract]
  The investigation of psychoneuroimmunological pathways represents a growing field of research . This paper reviews the current state of knowledge about a direct correlation of endogenous opioids and immunologically competent cells .
• Cell shape of polymorphonuclear leucocytes is influenced by opioids.
  Falke NE, Fischer EG (1985)
  Immunobiology 169,5:532-539 [PMID] [DOI]
      [Abstract]
  The effects of ß-endorphin(ß-End), an endogenous opioid, on shape changes in polymorphonuclear leukocyte (PMN) were tested in vitro. Cell shape changes indicate alterations of the functional status of the cells. Within 2 min ß-End, but not the opioid alkaloid levorphanol or the antagonist diprenorphine, induced a cell spreading . Subsequently ß-End and levorphanol (10⁸-8⁹ M), but not the dextrorotatory isomer, stimulated an elongation of the cells. Both effects of ß-End could be antagonized by diprenorphine in an equimolar concentration. Thus the effects were stereospecific and antagonizable. In this test system the morphological changes evoked by ß-End were equal to the effects of FMLP , a chemotactic substance, used as a reference. Our findings indicate that endogenous opioids might play a role in modulating the initial phase of the PMN's offensive behavior , presumably cell adherence and motility.
• Stereospecific opiate binding in living human polymorphonuclear leucocytes.
  Falke NE, Fischer EG, Martin R (1985)
  Cell Biol.int.Rep. 9,11:1041-1047 [PMID] [DOI]
      [Abstract]
  Living human polymorphonuclear leucocytes were incubated with various opiate agonists and antagonists in radioreceptor assays. Binding of the opiate antagonists 3H-naloxone and 3H-diprenorphine and of the benzomorphan 3H-ethylketocyclazocine was found at 4°C and at 37°C, 3H-naloxone binding was stereospecific. Binding of the opiate agonist 3H-dihydromorphine was present at 37°C but not at 4°C and had a different time course as compared to the antagonists. At both temperatures no specific binding of the proteolytic stable analogue 3H-D-Ala-D-Leu-enkephalin was found. Autoradiography showed an unspecific accumulation of 3H-naloxone inside the cells and a specific localization of grains at the cell membrane.
• Opioid effects in human granulocytes (PMN)
  Fischer EG, Falke NE (1985)
  Adv.Pharmacol.Res.Pract. Vol.2,Sect.3:243-250 (Akademiai Kiado, Budapest) [DOI]
      [Abstract]
  The interest in psychosomatic mechanisms induced us to look for connections between the opioid peptides occurring in blood and the polymorphonuclear leucocytes (PMNs). When we began these studies about four years ago it was really obscure to look for the influence of neuropeptides on the immune system. Now it is well established to do so (6). About 70% of the white blood cells are polymorpho- nuclear leucocytes (PMNs), often called granulocytes because of their vesicles. With macrophages they share a common precursor cell. Both, the PMNs and the macrophages can exert, to some extent, similar functions, such as phagocytosis, enzyme release, and migration. In addition, to these common functions, the macrophages are involved in specific immune responses. This paper will outline what is known to date about the opioid influence on granulocytes; in particular, the functional and binding studies.
• Opiate receptor mediated internalization of 125I-ß-endorphin in human polymorphonuclear leucocytes.
  Falke NE, Fischer EG (1986)
  Cell Biol.int.Rep. 10,6:429-435 [PMID] [DOI]
      [Abstract]
  The early events in the interaction of (¹²⁵I)-Tyr[27]- ß-endorphin with human polymorphonuclear leucocytes were investigated. Using ultrastructural autoradiography we found that the labeled peptide specifically bound to the plasma membrane and was internalized within two minutes of incubation at 37°C. Both processes could be inhibited by unlabeled ß-endorphin or by the opiate antagonist diprenorphine. This finding was confirmed by radioreceptorassays. With longer incubation times the specific association of the labeled ß-endorphin with the cells decreased. About 10% of the tracer was degraded within 10 min of incubation as shown by gel chromatography. The morphological changes induced by 125I-ß-endorphin in the granulocytes were investigated under the microscope. The labeled peptide had the same biological effect as unlabeled ß-endorphin.
• The influence of endogenous opioid peptides on venous granulocytes.
  Fischer EG, Falke NE (1986)
  (Plotnikoff NP et al.) Enkephalins and Endorphins: Stress and the Immune System. :263-272 (Plenum, New York) [DOI]
      [Abstract]
  Ameboid migrating phagocytes represent a phylogenetically ancient defense system. Amebocytes are found throughout the animal kingdom. All functions of the PMNs (aggregation, adherence, polarization, chemokinesis, chemotaxis, phagocytosis, pinocytosis, endocytosis, exocytosis) are primitive functions, as they occur in most of the protozoa. In mammals they appear in all embryonic cells and in some of the differentiated cells.
• Interaction of Met-enkephalin with human granulocytes.
  Fischer EG, Falke NE (1987)
  Ann.N.Y.Acad.Sci. 496:146-150 [PMID] [DOI]
      [Abstract]
  Effects of Met-enkephalin on cell shape and motility of human polymorphonuclear leucocytes (PMNs) have been found. Specific binding of tritium-labeled Met-enkephalin to the cells could not be demonstrated. There was a rapid proteolytic degradation of the peptide in the medium, followed by an uptake of the labeled tyrosine. The peptidase recognizes the N-terminal sequence of various endogenous opioid peptides. The protease inhibitors bestatin and bacitracin had only little effect on the the degradation of Met-Enk.
• Endogenous opioid peptides stimulate human phagocytes - functional and binding studies.
  Fischer EG, Falke NE (1987)
  Adv.Biosciences 66:373-379
      [Abstract]
  Endogenous opioid peptides and opioid alkaloids can modulate some functions of human phagocytes. There is good evidence for opioid receptors on these cells. Own studies will be presented in relation to the findings of other investigators in this field.
• Opioid peptides modulate immune functions. A review.
  Fischer EG (1988)
  Immunopharmacol.Immunotoxicol. 10,3: 265-326 [PMID] [DOI]
      [Abstract]
  In the past few years it has become evident that neuropeptides may be direct mediators in the modulation of the immune response and the unspecific defence by the brain. Lymphocytes have been thought to have opioid receptors and to respond to opioids with an increase in blastogenesis, cytotoxicity and factor release. Lymphocytes are said to release various neuropeptides. Furthermore, there are some unexplained effects of morphine on the immune system and of the immune system on morphine withdrawal. The purpose of this paper is to review what has been previously published in this field. The well established modulation of phagocyte functions by opioids will only be scanned.
• Endothelial cell-basement membrane interactions.
  Kirkpatrick CJ, Rixen H, Axer T, Schmitz U, Hollweg G, Klee D, Wajda R, Kampe M, Fischer EG, Mittermayer C. (1989)
  (Westerhof N, Gross DR) Vascular Dynamics and Physiological Perspectives. NATO Adv.Res.Workshop 166,Chap.10:135-148 (Plenum Publ.Corp., New York)
      [Abstract]
  One of the essential aspects of an intact blood vessel is the relationship existing between the endothelial cell layer and the underlying components of the basement membrane. These cell-matrix interactions take on particular significance in the case of damage to the endothelium, for example, in the course of inflammation or tumour cell invasion. The need to understand more about these interactions has been highlighted by the recent endeavours to 'seed' vascular prostheses with endothelial cells prior to implantation.
• In vitro studies on the expansion of endothelial cell monolayers on components of the basement membrane.
  Kirkpatrick CJ, Kampe M, Rixen H, Fischer EG, Ruchatz D, Mittermayer C (1990)
  Virchows Arch.(B) Cell Pathol. 58,3:207-213 [PMID]
      [Abstract]
  The purpose of the present study was to observe the expansion of a monolayer of endothelial cells over specific components of the basement membrane. This was performed in vitro in a monolayer expansion assay over 5 days. The control surface was uncoated glass in the form of coverslips. Test substances were coated at a concentration of 10 µg/ml. The highest expansion was obtained with a high molecular weight fragment mixture of collagen type IV (IV-F, consisting of 75, 120 and 140 KD fragments), followed by fibronectin. Collagens type I, III and IV tetramer gave similar results, less than fibronectin or collagen type IV-F, although all of the above basement membrane coatings promoted expansion significantly above that of the control (P less than 0.01). The poorest expansion was obtained with laminin, which was significantly less than the control. The pentapeptide GRGDS, related to the fibronectin cell binding region, gave expansion significantly below that of the intact fibronectin molecule, as did the intact collagen type IV molecule compared with type IV-F (P less than 0.025). This indicates that sequences of the fibronectin molecule other than the cell binding sequence may be involved in promoting endothelial cell expansion. In addition, the integrity of the collagen type IV molecule does not appear necessary for this effect. On the contrary, the higher movement on IV-F may represent an inherent repair mechanism in damaged endothelium. Autoradiographic studies show that endothelial cell proliferation at the expanding front is involved in the migration assay.
• Migration assay for endothelial cells in multiwells. Application to studies on the effect of opioids.
  Fischer EG, Stingl A, Kirkpatrick CJ (1990)
  J.Immunol.Meth. (1990) 128:235-239 [PMID] [DOI]
      [Abstract]
  An assay system is described which permits rapid and effective evaluation of endothelial cell repair, using cells growing in a monolayer. With this method it was possible to obtain highly significant results. For example, endothelial growth factor and heparin, significantly enhanced cell migration and/or proliferation, whereas beta-endorphin, an endogenous opioid, had no effect on the migration and/or proliferation of human umbilical vein endothelial cells. This model may be used to study the cell migration of a variety of cell types which under certain experimental conditions (e.g., irradiation) do not proliferate.
      click here, to read more about the assay on our website
• Opioid influence on the adherence of granulocytes to human umbilical vein endothelial cells in vitro.
  Fischer EG, Stingl A, Kirkpatrick CJ (1990)
  Cell Biol.int.Rep. 14,9:797-804 [PMID] [DOI]
      [Abstract]
  Recent studies revealed the existence of opioid receptors on human polymorphonuclear leukocytes (hPMN) and reported the effects of endogenous opioids on hPMN migration and adherence on glass or serum coated glass. Extending these studies, we investigated the influence of opioids on the adherence of hPMN to human umbilical vein endothelial cells as an in vitro model. Two different assay systems served to quantify the two basic events of adherence: attachment and spreading. hPMN in suspension were allowed to settle under the influence of ß-endorphin. After 30 and 240 sec the number of attached cells was enhanced 2.5-fold. Studying the spreading of cells, ß-endorphin increased the cell area 1.5-fold. Since adherence precedes the migration of hPMN through the endothelial cell layer towards foci of inflammation, the results suggest a modulatory role of endogenous opioids in defence mechanisms.
• Differential expansion of human endothelial monolayers on basement membrane and interstitial collagens, laminin and fibronectin in vitro.
  Kirkpatrick CJ, Kampe M, Fischer EG, Rixen H, Richter H, Mittermayer C (1990)
  Pathobiology 58,4:221-225 [PMID] [DOI]
      [Abstract]
  In this study the ability of a human endothelial cell monolayer to expand over specific components of the basement membrane and extracellular matrix was investigated over a 5-day period. The method was intended as a model to study the mechanisms of endothelial regeneration. All components were coated onto sterile coverslips at a concentration of 10 µg/ml. The highest expansion was obtained on fibronectin, laminin and collagen type III, all three being statistically significantly greater than on the uncoated control surface (0.002 greater than p greater than 0.0001). Collagens types I and IV and a high molecular weight fragment mixture of type IV (IV-F, consisting of 75, 120 and 140 kD fragments) elicited approximately similar expansion rates, significantly higher than the control (0.02 greater than p greater than 0.003), although significantly lower (approximately 15%) than collagen type III, fibronectin and laminin (p less than 0.001). The high monolayer expansion on collagen type III is surprising, as it is a relatively minor biosynthetic product of the endothelial cell. It could, however, be of significance in wound healing, in which endothelial cells come into contact with this interstitial collagen. In addition, the similar results obtained with collagens IV and IV-F indicate that expansion of the endothelial monolayer is not dependent on the integrity of the tetrameric structure of type-IV collagen.
      click here, to read more about the assay on our website
• Effect of fibrinogen fragments D and E on the adhesive properties of human granulocytes to vein endothelial cells.
  Fischer EG, Vogel P, Ziegler AS; Kirkpatrick CJ (1991)
  Haemostasis 21,3:141-146 [PMID] [DOI]
      [Abstract]
  In hyperfibrinolytic conditions, e.g. in disseminated intravascular coagulation or the adult respiratory distress syndrome, high levels of fibrinogen degradation products (FDPs) D and E are found in human plasma. This study investigates the influence of these fragments on cell attachment of human granulocytes in vitro. While leaving unaffected the adhesion of human umbilical vein endothelial cells (HUVEC) on gelatine-coated glass, both FDP fragments at 50 µg/ml inhibited granulocyte attachment to glass as well as to HUVEC monolayers. At the same concentration, the fragments diminished the superoxide release of stimulated granulocytes. These results suggest a modulatory role of pathologically elevated FDPs on the granulocyte function cascade.
• In vitro studies on PMN-independent endothelial cell damage in trauma: decrease of PMN-endothelial cell adherence by fibrinogen degradation products and disturbance of endothelial cell membrane integrity by trauma serum.
  Vogel P, v.d.Beek J, Marohl K, Fischer EG, Kirkpatrick CJ (1993)
  Eur.Surg.Res. 25,2:83-90 [PMID] [DOI]
      [Abstract]
  Trauma favors the development of adult respiratory distress syndrome (ARDS). Adherence of polymorphonuclear leukocytes (PMN) to endothelial cells (EC) with subsequent EC damage by the respiratory burst products and proteases of the PMN is thought to be one of the basic mechanisms in the pathogenesis of ARDS. Recent studies have shown that there might also be PMN-independent mechanisms of EC damage. It would speak for PMN-independent EC damage if in the state of risk for this damage factors were found which decrease PMN activity or if EC damage appeared without PMN. Because in trauma and sepsis pathologic coagulation with high levels of fibrinogen degradation products (FDP) is often diagnosed, we investigated whether FDP-D and FDP-E might influence PMN adherence to EC. We also investigated whether serum of traumatized patients might provoke EC damage in a PMN-independent system in vitro. To achieve this we evaluated the viability of EC using a fluorescence staining method. We found that both FDP-D and FDP-E decreased PMN adherence to human EC significantly (p < 0.01) at a concentration of 50 µg/ml. Furthermore we found that EC membrane integrity can be disturbed by serum of trauma patients. These results suggest that in trauma also PMN-independent mechanisms are important for EC damage.

Neurologie :

• Glutamic acid diethyl ester induces catalepsy in rats. A new model for schizophrenia ?
  Kornhuber J, Fischer EG (1982)
  Neurosci.Lett. 34,3:325-329 [PMID] [DOI]
      [Abstract]
  The glutamate antagonist glutamic acid diethyl ester is found to produce catalepsy in rats, when administered into the lateral ventricle. Since the cerebrospinal fluid content of glutamate is reduced in patients with schizophrenia, the central effects of glutamate antagonists are a possible experimental model for schizophrenia.
• Failure to detect dopamine receptor IgG autoantibodies in sera of schizophrenic patients.
  v.Kirchbach A, Fischer EG, Kornhuber HH (1987)
  J.Neural.Transm. 70,1-2:175-179 [PMID] [DOI]
      [Abstract]
  Autoantibodies against dopamine receptors in schizophrenic patients have been postulated. IgG was fractionated from sera of 15 schizophrenic patients (DSM III) in an acute episode. However, 3H-spiperone binding to dopamine receptors was not inhibited by this fraction.
• T-Lymphocyte subpopulations in multiple sclerosis - Do they help to judge immunosuppressive therapy ?
  Henneberg A, Fischer EG, Kornhuber HH (1988)
  Eur.Arch.Psychiatry Neurol.Sci. 238,2:94-96 [PMID]
      [Abstract]
  T-cell subpopulations have been tested in multiple sclerosis (MS) patients before and after cyclophosphamide (n=38), corticotropin (n=37), and physiotherapeutical (n=32) treatment. There were no specific changes of subset ratios immediately after immunosuppressive treatment. However, T-cell subpopulations showed great day-to-day variations in MS patients.
• Are there antilymphocyte autoantibodies in multiple sclerosis patients ?
  Fischer EG, Ahlers F, Kornhuber HH, Henneberg A (1989)
  J.Neurol.Sci. 93,2-3:319-322 [PMID] [DOI]
      [Abstract]
  Immunoglobulins were separated from sera of 40 multiple sclerosis (MS) patients and 40 healthy controls by density and affinity chromatography. In IgM and IgG fractions of 40 MS patients and 40 controls no lymphocyte-specific binding could be detected by the help of FITC-conjugated anti-µ and anti-Fc antibodies.