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Biomedical subjects

M Köller

Publications and source records attributed to M Köller.

At least 55 records · Page 3Linked to original sources
PubMed1995

Expression of the adhesion molecule CD11b and polymerization of actin by polymorphonuclear granulocytes of patients endangered by sepsis.

The integrin CD11b is an important adhesion molecule mediating the transendothelial migration of circulating polymorphonuclear granulocytes into an inflammatory region. The expression of CD11b is closely related to the ability to polymerize actin, a major component of the cytoskeleton within the phagocyte. In this study we compared the CD11b expression as well as the polymerization of actin of isolated neutrophils from patients endangered by sepsis with cells from healthy donors. The patient population was subdivided into a group of patients with severe thermal injuries and a group of patients who were admitted to an intensive care unit on suspicion of sepsis. The following results were obtained: (1) cells from burn patients, but not from non-burn patients, showed a reduced basal expression of CD11b during the first week after the burn trauma; (2) stimulation with the chemotactic peptide formyl-Met-Leu-Phe (FMLP) led to a strong overexpression of CD11b on the cells from the burn patients, this effect was not observed using cells of the second subgroup; (3) the content of polymerized actin was reduced within resting and stimulated cells from burn patients during the first 2 weeks postinjury, non-burn patient cells showed an enhanced F-actin content within the first week; (4) the ability of burn and non-burn patient cells to polymerize actin after stimulation with FMLP was slightly impaired during the first week post injury/admission. The results demonstrate that cells from patients endangered by sepsis show dysfunctions on the level of adhesion molecule expression and the strongly related actin polymerization.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1995

Influence of a pre-operative enteral supplement on functional activities of peripheral leukocytes from patients with major surgery.

Following severe trauma or major surgery patients develop functional alterations of host defense mechanisms which contribute an enhanced susceptibility towards microbial infections. Several studies have demonstrated that a specialized nutritional regimen may improve immune functions. We analyzed leukocyte functions from 40 patients undergoing major upper gastrointestinal surgery in a randomized placebo-controlled double-blind study. Patients were divided into two groups, one received 5 days pre-operatively an orally given experimental supplement enriched with omega-3-fatty acids, arginine, and ribonucleic acid (RNA), the other an isocaloric, control supplement. The experimental group generated significantly more leukotriene B(5) (LTB(5)) as compared to the control group. In contrast, the capacity to generate leukotriene B(4) (LTB(4)) as well as the synthesis of interleukin-8 (IL-8) was not significantly different in both groups. Additionally, lymphocyte/monocyte proliferation was analyzed and donor specific heterogeneities were observed; but no significant differences were found between the two nutritional regimens.

Journal Article↗
PubMed1994

Ligation of N-acetylgalactosamine-containing structures on rat bone marrow cells enhances myeloid differentiation and murine granulocyte-macrophage colony-stimulating factor-induced proliferation.

Previously we have reported the differentiation-dependent expression of a soybean agglutinin (SBA)-binding structure on rat bone marrow cells (BMCs) during their differentiation into macrophages (m phi s). In the present study we tried to analyze the functional role of the SBA-binding structure in BMC proliferation and differentiation. Addition of SBA to BMC cultures driven into m phi differentiation by recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), resulted in a two- to threefold increased proliferation rate compared with rmGM-CSF alone. However, the number of colonies in methyl cellulose was not increased by SBA. The effect of SBA was dose dependent (from 4 to 83 pM SBA), with a maximum effect at 83 pM. Experiments to detect a possible synergistic effect of additional cytokines produced by BMC after SBA treatment were inconclusive. The enhancing effect of SBA was also seen when high-density cells, which did not proliferate in response to rmGM-CSF (mainly granulocytes), were removed. Therefore, SBA may increase the CSF reactivity of responsive m phi progenitor cells directly by binding to N-acetylgalactosamine residues on their surface.

Acetylgalactosamine↗
PubMed1994

Development of a carbohydrate antigen during storage of red cells.

BACKGROUND: Changes in surface antigens during the aging of red cells led to the expression of epitopes that can induce an immune response. Recently, irregular antibodies detected in the sera of two patients agglutinated in vitro aged red cells. STUDY DESIGN AND METHODS: The aging of red cells during storage was examined by flow cytometric analysis using fluorescein isothiocyanate-labeled lectins, fluorescein isothiocyanate-labeled anti-human IgG, and fluorescein isothiocyanate-labeled IgM. RESULTS: Red cells stored for 1 day and 21 days exhibited no difference in the binding of wheat germ agglutinin, Ulex europaeus agglutinin, or concanavalin A. Only soybean agglutinin showed increased binding to old red cells. IgM antibodies present in the sera of two patients induced strong agglutination of stored red cells, but not of fresh red cells of the same or compatible ABO blood groups. The binding of these antibodies did not involve known red cell antigens and could be significantly inhibited by galactose and mannose in a dose-dependent manner. Staining of red cells with sera from both patients indicated that the antibodies recognized the same structure on stored red cells. The number of binding sites on red cells stored for 21 days was between 7,000 and 10,000 per cell. CONCLUSION: These results demonstrate that, during storage of red cells, gradual expression of galactosyl residues on the red cell membrane occurs.

Antigens, Surface↗
PubMed1994

Activation of human effector cells by different bacterial toxins (leukocidin, alveolysin, and erythrogenic toxin A): generation of interleukin-8.

We analyzed the transcription and release of interleukin-8 (IL-8) from human polymorphonuclear granulocytes (PMNs) and a lymphocyte-monocyte-basophil (LMB) cell population stimulated for different time periods (30 min to 16 h) with pore-forming bacterial toxins (Panton-Valentine leukocidin [Luk-PV] and alveolysin [Alv]) as well as with the erythrogenic toxin A (ETA) as a superantigen. At high toxin concentrations (500 ng/10(7) cells), Luk-PV and Alv led to a decreased IL-8 generation from LMBs within the first 30 min; with PMNs, a slight increase in IL-8 release was observed. Under these conditions, stimulation with ETA did not lead to an altered cellular IL-8 release. At lower concentrations (5 and 0.5 ng/10(7) cells), all three toxins led to a continuous increase (over 16 h) in IL-8 release and IL-8 mRNA expression of PMNs and LMBs. Preincubation of the cells with the protein tyrosine kinase inhibitors lavendustin A and tyrphostin 25 led to a reduction of the toxin-mediated effects on IL-8 release and IL-8 mRNA expression when Luk-PV and Alv were used as stimuli. In contrast, IL-8 synthesis in cells which were stimulated with ETA was not influenced by protein tyrosine kinase inhibition. From our data, one may suggest that multiple pathways for IL-8 production are operative in human leukocytes.

Bacterial Proteins↗
PubMed1994

GTP-binding proteins are involved in the modulated activity of human neutrophils treated with the Panton-Valentine leukocidin from Staphylococcus aureus.

Significant amounts of leukotriene B4 (LTB4) are generated by human polymorphonuclear neutrophils (PMNs) after incubation with the Panton-Valentine leukocidin (Luk-PV) from Staphylococcus aureus V8 strains. We showed that GTP-binding proteins (G proteins) are involved in the Luk-PV-activated signal transduction of PMNs. ADP-ribosylation of heterotrimeric G proteins by cholera and pertussis toxins decreased the Luk-PV-induced LTB4-generation. In contrast, ADP-ribosylation of the low-molecular-weight G proteins rho and rac by Clostridium botulinum exoenzyme C3 increased the Luk-PV-induced LTB4 synthesis. The subsequent stimulation of Luk-PV-treated PMNs by either calcium ionophore A23187, sodium fluoride, or formylmethionyl-leucyl-phenylalanine was significantly inhibited. This decrease was paralleled by a loss of G-protein functions, including GTPase activity and GTP-binding capacity. An increase of G-protein functions was obtained with low amounts of Luk-PV. In addition to the modulated G-protein functions, ADP-ribosylation of 24-, 40-, and 45-kDa proteins by Luk-PV was detected. As shown in control experiments, the ADP-ribosylated 24-kDa proteins were not substrates for C. botulinum exoenzyme C3. Introduction of ras p21 into digitonin-permeabilized PMNs was without effect on subsequent Luk-PV stimulation. In addition, the translocation of ras p21, ras GAP, and 5-lipoxygenase into the membrane of Luk-PV-treated PMNs, as well as the expression of chemotactic membrane receptors for LTB4 and formylmethionyl leucyl phenylalanine, was significantly diminished.

Arachidonate 5-Lipoxygenase↗
PubMed1994

Leukotriene B4 generation and DNA fragmentation induced by leukocidin from Staphylococcus aureus: protective role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF for human neutrophils.

We studied the effect of leukocidin from Staphylococcus aureus V8 strains (Luk-PV) on the generation of Leukotriene B4 (LTB4) and its metabolites from human polymorphonuclear neutrophils (PMNs). Significant amounts of LTB4 were generated by PMNs after leukocidin exposure in a time- and dose-dependent manner, as shown by reversed-phase high-performance liquid chromatography analysis. In this regard, the S and F components of leukocidin acted synergistically. The calcium ionophore A23187 induced LTB4 generation, and the metabolism of exogenously added LTB4 into biologically less active omega-oxidated compounds was significantly decreased after leukocidin exposure. Priming of PMNs with granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF prior to leukocidin exposure substantially increased toxin- and calcium ionophore A23187-induced LTB4 formation. The inhibitory effects of leukocidin on mediator release were accompanied by membrane damage and DNA fragmentation, which were both restored after pretreatment with GM-CSF. The data suggest that the presence of costimulatory priming factors such as GM-CSF or G-CSF in the microenvironment of an inflammatory focus determines the pathophysiological effects induced by S. aureus leukocidin.

Calcimycin↗
PubMed1994

Effect of elevated growth hormone concentrations on the phenotype and functions of human lymphocytes and natural killer cells.

Over the past decades, strong evidence has accumulated that growth hormone (GH) has immunostimulatory properties. Therefore, an investigation was conducted on 10 acromegalic patients and 9 age- and sex-matched healthy controls to determine whether plasma GH concentrations correlate with changes in several immune parameters, including serum concentrations of immunoglobulins, lymphocyte subsets, lymphocyte transformation with phytohemagglutinin (PHA), natural killer (NK) cell activity as well as phagocytic and metabolic burst activity. While NK cell activity, serum concentrations of immunoglobulins (IgG, IgM, IgA) and metabolic burst activity were within the normal range in both groups, a significantly enhanced phagocytic activity was observed in the acromegalic patients. Surface markers on T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD19) and NK cells (CD16/56) were normal in both groups; however, in the acromegalic subjects, CD4+ and CD8+ cells showed a significant higher expression of transferrin receptors (CD71), indicating enhanced T-cell activity. The lymphocyte transformation response to PHA at the highest concentration tested showed a tendency to be elevated in acromegalics; however, the difference failed to be significant. Long-lasting and pronounced elevation of GH in acromegaly induces significantly enhanced phagocytic activity, but only negligible changes in most patients in lymphocyte phenotype and in the lymphocyte response to PHA.

Acromegaly↗
PubMed1994

Influence of suramin on the expression of Fc receptors and other markers on human monocytes and U937 cells, and on their phagocytic properties.

Suramin, a polyanionic and polycyclic compound, was initially used for the treatment of trypanosomiasis and onchocerciasis. In the last decade, it has been used in therapy of cancer and acquired immune deficiency syndrome (AIDS). The influence of suramin on the expression of various markers by human mononuclear phagocytes is not known and was, therefore, presently investigated. Suramin inhibited the proliferation of U937 cells and mitogen-induced T-cell proliferation in a dose-dependent manner. The constitutive and cytokine-driven expression of Fc receptors for IgG (Fc gamma RI and Fc gamma RII), IgE (Fc epsilon RII) and IgA (Fc alpha R) on blood monocytes and U937 cells was suppressed by suramin. The basal level, as well as cytokine-induced major histocompatibility complex (MHC) class II antigens, was markedly diminished on suramin-treated monocytes. Furthermore, suramin dramatically reduced expression of CD14 and partially reduced complement receptor type 3 (CR3) and CR4 expression on monocytes. In contrast, suramin slightly induced MHC class I antigens on monocytes and CD71 on U937 cells. The capacity of monocytes to phagocytose IgG-sensitized ox erythrocytes, opsonized Escherichia coli, or fluorescein isothiocyanate (FITC)-conjugated latex beads was significantly inhibited. Northern blot analysis showed that the amount of Fc epsilon RII-specific mRNA was only partially reduced, suggesting that other mechanisms may be involved in the regulation of Fc epsilon RII expression. Our data demonstrate that suramin suppresses the expression of various cell-surface structures on human mononuclear phagocytes and impairs their phagocytic capacity.

Blotting, Northern↗
PubMed1994

[Individual differences in solving spatial problems of the IST and IST-70 subtest on "cube problems"].

Spatial ability is one of the primary mental abilities which has been subject of many empirical studies--especially in the factor analytical research. Analysing the mental processes when solving space tasks, e. g. by means of retrospective verbal reports, two different strategies can be distinguished. The first strategy (called "holistical" strategy) can be described as a mental rotation of the given stimulus, the second one (called "analytical" strategy) is characterised by nontransformal mental processes, e. g. pattern matching processes. In order to identify those different strategies, test items are required, which have different solution probabilities when being solved with different strategies. The "cube tasks" of the IST and IST-70 by Amthauer (1953, 1970) are of this type, as Putz-Osterloh (1977) has found in an experiment. The hypothesis of individual differences in solving space tasks was tested in two different samples. First the "cube tasks" of the IST-70 were administrated to 264 applicants for the pilot job. Data analyses using the mixed-Rasch-model (Rost, 1990) confirmed the hypothesis of an "analytical" and "holistical" strategy. In the second study 2558 pupils of the 7th grade were tested with the "cube tasks" of the IST. A latent class analysis of their response patterns revealed basically the "holistical" and "analytical" strategy and, in addition, four strategies which can be explained by motivational factors.

Adolescent↗
PubMed1993

GTP-binding proteins in polymorphonuclear granulocytes of severely burned patients.

In order to study the biochemical mechanism underlying the cellular dysfunctions of polymorphonuclear granulocytes (PMNs) from severely burned patients, we analyzed the role of GTP-binding proteins (G-proteins) in PMNs from 11 burned patients. Our data demonstrate a significant enhancement of the basal GTPase activity within unstimulated neutrophils of severely burned patients compared to cells from healthy donors. This enhancement was significant within 4 weeks after the trauma, followed by a return to control levels. The increase in GTPase activity correlated with enhanced expression of the small G-protein Ras and the regulatory Ras-GTPase activating protein (Ras-GAP) compared to that in healthy donor cells. However, expression of the Ras-related protein Rap1, which is involved in initiation of the respiratory burst, was reduced. The observed changes in G-protein activity and expression impair the signal transduction cascade as well as bacterial killing and may lead to high susceptibility toward infections and finally to septic conditions.

Adult↗
PubMed1993

Induction of heat-shock proteins by bacterial toxins, lipid mediators and cytokines in human leukocytes.

We studied the influence of a lipid mediator (12-hydroxyeicosatetraenoic acid, 12-HETE), cytokines (IL-6 and TNF-alpha) and different bacterial toxins (alveolysin; exfoliative toxin; toxic shock syndrome toxin 1, TSST-1 and erythrogenic toxin A, ETA) on the expression of heat shock proteins (hsps) in isolated human leucocytes. 12-HETE induces the expression of individual heat shock proteins (65- and 83 kDa) protein in human leukocytes (lymphocytes, monocytes, basophilic granulocytes; LMBs). As was shown by Western blotting (anti-hsp72), IL-6 or TNF-alpha induced hsps preferentially in human LMBs and PMNs, respectively. Among the toxins, ETA and TSST-1 were potent inducers of hsps at low toxin concentrations (10 ng/ml). Alveolysin led to the expression of hsps at hemolytic concentrations (1 HU; 700 ng/ml) whereas at subhemolytic concentrations (7 ng/ml), no heat shock response was observed. The induction of heat shock proteins was also accompanied by increased mRNA levels for hsp70 as determined by PCR analysis. In contrast, exfoliative toxin led to a reduction of the hsp signal in PMNs as determined by Western blotting. Finally, it was demonstrated that PMNs which had been pretreated with TNF-alpha and therefore expressed intracellular hsps were more resistant to cytolytic attack by leukocidin than untreated cells.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Staphylococcus aureus toxic shock syndrome toxin 1 and Streptococcus pyogenes erythrogenic toxin A modulate inflammatory mediator release from human neutrophils.

We studied the influence of staphylococcal toxic shock syndrome toxin 1 and streptococcal erythrogenic (pyrogenic) toxin A (ETA) on intact and digitonin-permeabilized human polymorphonuclear granulocytes (PMNs). As was shown by reversed-phase high-performance liquid chromatography analysis, toxic shock syndrome toxin 1 or ETA alone, in the absence of any additional stimulus, did not induce the generation of the chemoattractant leukotriene B4 (LTB4) from PMNs in a wide range of concentrations. In addition, pretreatment of intact PMNs with either toxin potentiated formyl-methionyl-leucyl-phenylalanine (fMLP)- and washed Staphylococcus aureus cell-induced generation of LTB4 in a time- and dose-dependent manner. This increase included LTB4 as well as its inactive omega-oxidated compounds. Further studies revealed evidence that toxin exposure was accompanied by enhanced cellular receptor expression for fMLP as well as for LTB4. The intrinsic GTPase activity of membrane fractions was modulated by both toxins. Short-term incubation with ETA increased the GTPase activity of PMNs up to 141%. Inhibitory effects were obtained when GTP-binding protein functions were stimulated with sodium fluoride (NaF). In addition, specific binding of Gpp(NH)p to GTP-binding protein was inhibited by both toxins during the first 10 min of incubation and was restored at later times of incubation. Our data therefore suggest that both toxins significantly affect the signal transduction pathways of human PMNs, which results in immunomodulatory functions.

Bacterial Proteins↗
PubMed1992

Priming mechanisms and induction of heat shock proteins in human polymorphonuclear granulocytes induced by eicosanoids and cytokines.

Priming of human polymorphonuclear granulocytes (PMNs) with cytokines (IL-3, IL-6, TNF-alpha) followed by a subsequent stimulation (FMLP) led to an enhanced polymerization of actin and GTPase-activity which correlated to a loss of ras immunoreactivity and an increased expression of Rab proteins. Furthermore TNF-alpha and 12-HETE induced the heat shock proteins (hsp 70 family) in PMNs as was demonstrated by metabolic radiolabeling and Western blotting (anti-hsp 72). This activation of the stress response exerted a protective function towards a subsequent lytic attack by a bacterial cytolysin (leukocidin).

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

Bacterial toxins induce heat shock proteins in human neutrophils.

We studied the influence of different bacterial toxins (alveolysin; toxic shock syndrome toxin 1, TSST-1 and erythrogenic toxin A, ETA) on the expression of heat shock proteins (hsps) in isolated human polymorphonuclear granulocytes (PMNs). As was shown by Western blotting (anti-hsp72) ETA and TSST-1 were potent inducers of hsps at low toxin concentrations (10 ng/ml). Alveolysin led to the expression of hsps at hemolytic concentrations (1 HU; 700 ng/ml) whereas at subhemolytic concentrations (7 ng/ml) no heat shock response was observed. The induction of heat shock proteins was also accompanied by increased mRNA levels for hsp70 as was determined by PCR-analysis.

Bacterial Proteins↗
PubMed1991

12-Hydroxyeicosatetraenoic acid (12-HETE) induces heat shock proteins in human leukocytes.

12-Hydroxyeicosatetraenoic acid (12-HETE) induces the expression of individual heat shock proteins in human leukocytes (lymphocytes, monocytes, basophil granulocytes; LMBs). Metabolic radiolabeling of LMBs revealed that exogenous 12-HETE (20 ng) led to the expression of a 65- and 83kDa protein. Immunoreactivity towards the 65kDa protein was commonly detected. In contrast, after heat shock treatment and predominantly after incubation with 12-HETE significant immunoreactivity (anti-hsp72) was detected in the lower molecular weight range whereas immunoreactivity (anti-hsp90, AC88) was only observed after heat shock treatment of LMBs.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗