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N Suttorp

Publications and source records attributed to N Suttorp.

At least 55 records · Page 3Linked to original sources
PubMed1998

Rho protein inhibition blocks protein kinase C translocation and activation.

Small GTP-binding proteins of the Ras and Rho family participate in various important signalling pathways. Large clostridial cytotoxins inactivate GTPases by UDP-glucosylation. Using Clostridium difficile toxin B-10463 (TcdB) for inactivation of Rho proteins (RhoA/Rac/Cdc42) and Clostridium sordellii lethal toxin-1522 (TcsL) for inactivation of Ras-proteins (Ras/Rac/Ral, Rap) the role of these GTPases in protein kinase C (PKC) stimulation was studied. Phorbol-myristate-acetate (PMA) induced a rapid PKC translocation to and activation in the particulate cell fraction as determined by PKC-activity measurements and Western blots for PKC alpha. These effects were blocked by TcdB inhibiting Rho proteins in endothelial cells, but not in TcsL-treated cells (i.e., cells without Ras activity), suggesting that Rho GTPases (RhoA and/or Cdc42) are the most likely GTP-binding proteins responsible for PKC activation. The Rho requirement for PKC activation/translocation was also verified for human epithelial cells and for lipopolysaccharide-stimulated endothelial cells. In summary, the data presented indicate that Rho protein inhibition blocked PKC translocation/activation in endothelial and epithelial cells.

Animals↗
PubMed1998

Interaction of human neutrophils with airway epithelial cells: reduction of leukotriene B4 generation by epithelial cell derived prostaglandin E2.

Airway epithelial cells (AEC) play an active role in the regulation of inflammatory airway disease. In the present study we analyzed the interaction of AEC with polymorphonuclear leukocytes (PMN) in coincubation with respect to their arachidonic acid (AA) metabolism using reversed phase-HPLC and post-HPLC-ELISA. Primary cultures of porcine AEC released predominantly PGE2, PGF2a, and 15-hydroxyeicosatetraenoic acid (15-HETE), whereas the major human PMN-derived AA metabolite was the chemotactic factor leukotriene B4 (LTB4). In AEC-PMN cocultures stimulated with the calcium ionophore A23187, PMN-related 5-lipoxygenase products were decreased by 45%. This reduction in LTB4 formation in the presence of AEC was mainly due to PGE2 generated by the epithelial cells, whereas 15-HETE made a minor contribution. Most of the effect was inhibited by AEC pretreatment with acetylsalicylic acid and restored by addition of equivalent amounts of exogenous PGE2. LTB4 degradation was not enhanced in PMN-AEC coincubations. Moreover, reduction of LTB4 formation in this system did not require an intimate cell-to-cell contact as shown by studies involving filter membranes for PMN-AEC separation. Superoxide anion concentrations were also decreased in PMN-AEC coincubations; this effect, however, was unrelated to PGE2 for quantitative reasons and was probably due to O2- degradation by epithelial cells. In summary, epithelially derived PGE2 is the major mediator in the coincubation of porcine AEC and human PMN that downregulates neutrophil responses by activating receptors on the neutrophil. A minor contributor in this course of PMN-AEC interaction may be the 15-HETE transcellular pathway. Overall, airway epithelium appears to play an antiinflammatory role by damping the proinflammatory potential of neutrophils.

Animals↗
PubMed1998

VEGF induces hyperpermeability by a direct action on endothelial cells.

Vascular endothelial growth factor (VEGF) is a key regulator of vasculo- and angiogenesis. Earlier studies demonstrated a permeability-increasing effect of VEGF in skin tests, leading to its other name, vascular permeability factor. We wondered whether VEGF-induced hyperpermeability was a direct effect of VEGF on endothelial cells and studied the permeability of human and porcine endothelial cell monolayers in a well-characterized in vitro system. VEGF increased the hydraulic conductivity up to 20-fold and simultaneously decreased the albumin reflection coefficient. This effect occurred after a delay of 150 min, although VEGF-induced early endothelial cell activation was verified by enhanced inositol phosphate accumulation within 5 min and increased P-selectin expression within 15 min. Platelet-derived growth factor and granulocyte-macrophage colony-stimulating factor, two endothelial cell nonspecific mitogens, also stimulated phosphatidylinositol metabolism and P-selectin expression; however, they had no effect on endothelial permeability. The increase in intracellular cyclic nucleotide levels of human endothelial monolayers abolished VEGF-induced endothelial hyperpermeability. In summary, VEGF increased endothelial permeability by a direct action on endothelial cells. Based on the pattern of endothelial cell activation by growth factors, VEGF appears to be a unique stimulus.

Capillary Permeability↗
PubMed1997

Human endothelial cell activation and mediator release in response to the bacterial exotoxins Escherichia coli hemolysin and staphylococcal alpha-toxin.

Escherichia coli hemolysin (HlyA) and Staphylococcus aureus alpha-toxin are membrane-perturbating bacterial exotoxins that have been implicated as significant virulence factors in human diseases. We investigated the capacity of these toxins to cause cell activation and mediator release in human endothelial cells, compared with the efficacies of thrombin and the Ca2+ ionophore A23187. Concentration ranges tested were 1 to 1000 ng/ml (HlyA), 0.01 to 10 micro/ml (alpha-toxin), 0.01 to 10 U/ml (thrombin), and 0.01 to 10 microM (A23187). All stimuli caused dose-dependent generation of platelet-activating factor, nitric oxide, and prostaglandin I2. HlyA and thrombin effected time- and dose-dependent accumulation of large quantities of inositol phosphates, with maximum effects at 100 ng/ml and 1 U/ml, respectively. Corresponding time course and dose dependency were noted for HlyA-elicited diacylglycerol formation. In contrast, only the highest concentrations of alpha-toxin (10 microg/ml) and A23187 (10 microM) effected some moderate inositol phosphate accumulation, and this was suppressed in the presence of the platelet-activating factor antagonist WEB 2086. Metabolic and secretory responses elicited by alpha-toxin were dependent on the presence of extracellular Ca2+. We conclude that both HlyA and alpha-toxin are potent inductors of inflammatory and vasodilatory mediators in human endothelial cells. HlyA-elicited effects may proceed predominantly via activation of the phosphatidylinositol hydrolysis-related signal transduction pathway, whereas transmembrane Ca2+ flux appears to be the major event underlying the release of mediators in response to alpha-toxin. These toxin properties may contribute to vasoregulatory and inflammatory disturbances encountered in states of severe infection and sepsis.

Animals↗
PubMed1997

Listeria monocytogenes potently induces up-regulation of endothelial adhesion molecules and neutrophil adhesion to cultured human endothelial cells.

Infection of endothelial cells by Listeria monocytogenes is an essential step in the pathogenesis of listeriosis. Listeriolysin (Hly) is one of its major virulence factors. In the early phase of the disease polymorphonuclear leukocytes (PMN) substantially contribute to the nonspecific anti-listerial resistance. We characterized the effects of L. monocytogenes on the expression of endothelial adhesion molecules and on subsequent PMN adhesion to cultured HUVEC. P-selectin, E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were up-regulated in HUVEC after cell incubation with L. monocytogenes (wild type), but not with the nonpathogenic Listeria innocua strain. P-selectin expression peaked after 30 min and could be mimicked with similar kinetics by exposure to L. innocua engineered to produce large amounts of Hly or by addition of purified Hly. Listeriolysin production, however, was not necessary for an up-regulation of E-selectin after 6 h or of ICAM-1 and VCAM-1 after 18 to 24 h in HUVEC, because L. monocytogenes defective for Hly synthesis was almost as effective as the wild type. Listeria-induced up-regulation of endothelial adhesion molecules was accompanied by an increased binding of PMN to infected HUVEC. PMN adhesion was significantly reduced in the presence of anti-beta2 integrin, anti-E-selectin, and anti-ICAM-1, but not anti-VCAM-1 Abs. Our data indicate that infection of endothelial cells with L. monocytogenes induced up-regulation of adhesion molecules by two different mechanisms: a Hly-dependent up-regulation of P-selectin and a Hly-independent expression of E-selectin, ICAM-1, and VCAM-1. The ability of L. monocytogenes to stimulate PMN adhesion to endothelial cells may be an important mechanism in the pathogenesis of severe listeriosis.

Cell Adhesion↗
PubMed1997

Glucosylation of small GTP-binding Rho proteins disrupts endothelial barrier function.

The endothelial cytoskeleton is important for the regulation of endothelial barrier function. Small GTP-binding Rho proteins play a central role in the organization of the microfilament system. Clostridium difficile toxin B (TcdB) inactivates Rho proteins by glucosylation at Thr-37. We used TcdB as a probe to study the role of Rho proteins in the regulation of endothelial barrier function. TcdB time (50-170 min) and dose (10-100 ng/ml) dependently increased the hydraulic conductivity of cultured porcine pulmonary artery endothelial cell monolayers approximately 10-fold. Simultaneously, the albumin reflection coefficient decreased substantially from 0.8 to 0.15. Before endothelial hyperpermeability, TcdB reduced F-actin content in a dose-dependent manner, whereas G-actin content remained unchanged. Finally, we proved that TcdB caused dose (5-100 ng/ml)- and time-dependent glucosylation of Rho proteins in endothelial cells. Phalloidin, which stabilizes filamentous actin, prevented the effect of TcdB on endothelial permeability. In contrast to thrombin-, hydrogen peroxide-, or Escherichia coli hemolysin-induced hyperpermeability, the elevation of cyclic nucleotides did not block TcdB-related permeability. The data demonstrate a central role of small GTP-binding Rho proteins for the control of endothelial barrier function.

Actins↗
PubMed1996

Escherichia coli hemolysin and Staphylococcus aureas alpha-toxin potently induce neutrophil adhesion to cultured human endothelial cells.

Adhesion of polymorphonuclear leukocytes (PMN) to endothelial cells is an essential step in inflammatory reactions. We characterized the effects of two important bacterial exotoxins, Escherichia coli hemolysin (HlyA) and Staphylococcus aureus alpha-toxin (S. alpha-toxin) on PMN adhesion to cultured HUVEC. Both toxins increased adherence of human PMN to HUVEC in a dose- and time-dependent manner, peaking after 30 min at 0.01 hemolytic units/ml HlyA or 0.5 microg/ml S. alpha-toxin. Pretreatment of HUVEC with anti-P-selectin mAbs or of PMN with anti-CD11b/CD18 mAb reduced HlyA- and S. alpha-toxin-related cell adhesion significantly. Increased P-selectin expression on toxin-treated endothelial cells was demonstrated by cell surface ELISA. Compared with endotoxin, HlyA and S. alpha-toxin did not induce the expression of E-selectin, ICAM-1, or VCAM-1. FACS analysis showed increased CD11b/CD18 expression on HlyA-, but not on S. alpha-toxin-stimulated PMN. Platelet-activating factor, an important costimulatory factor for PMN adhesion and activation, was also active in the exotoxin-stimulated adhesion system, as evidenced by studies using the platelet-activating factor receptor antagonist BN50727. HPLC analysis of endothelial cell extracts confirmed enhanced toxin-mediated PAF synthesis. The capacity of exotoxins to stimulate PMN adhesion to endothelial cells may be relevant in patients with severe local or systemic bacterial infections.

Azepines↗
PubMed1996

Hyperpermeability of pulmonary endothelial monolayer: protective role of phosphodiesterase isoenzymes 3 and 4.

The regulation of endothelial permeability is poorly understood. An increase in endothelial permeability in the pulmonary microvasculature, however, is critical in noncardiogenic pulmonary edema and other diffuse inflammatory reactions. In the present study thrombin and Escherichia coli hemolysin (HlyA), a membrane-perturbing bacterial exotoxin, were used to alter hydraulic permeability of porcine pulmonary artery and human endothelial cell monolayers. We also investigated the pharmacological approach of adenylyl cyclase activation/phosphodiesterase (PDE) inhibition to block endothelial hyperpermeability. Thrombin (1-5 units/ml) and HlyA (0.5-3 hemolytic units/ml) dose and time dependently (> 15 min) increased endothelial permeability. Forskolin, cholera toxin, and prostaglandin E1, which all stimulate adenylyl cyclase activity, abrogated this effect. One mM dibutyryl cAMP, a cell membrane-permeable cAMP analogue, was similarly active. Endothelial hyperpermeability was also reduced dose dependently by inhibitors of different PDE isoenzymes (motapizone, rolipram, and zardaverine, which block PDE3 and/or PDE4). The effectiveness of PDE inhibitors was increased in the presence of adenylyl cyclase activators. Analysis of cyclic nucleotide hydrolyzing PDE activity in lysates of human umbilical vein endothelial cells showed high activities of PDE isoenzymes 2, 3, and 4. Consistent with the functional data PDE3 and PDE4 were the major cAMP hydrolysis enzymes in intact endothelial cells. We conclude that the hyperpermeability of pulmonary endothelial monolayers, evoked by thrombin or HlyA, can be blocked by the simultaneous activation of adenylyl cyclase and inhibition of PDEs, especially of PDE3 and PDE4. The demonstration of PDE isoenzymes 2-4 in human endothelial cells will help optimize this therapeutic approach.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Role of nitric oxide and phosphodiesterase isoenzyme II for reduction of endothelial hyperpermeability.

Regulation of endothelial permeability is poorly understood. Previous studies have shown that endothelial cells contain phosphodiesterase (PDE) isoenzymes II-IV and that simultaneous adenylate cyclase activation and/or PDE inhibition blocked endothelial hyperpermeability (J.Clin.Invest. 91: 1421-1428, 1993). We now focused on a possible role for guanosine 3',5'-cyclic monophosphate (cGMP)-dependent mechanisms and studied H2O2-exposed porcine pulmonary artery endothelial cell monolayers. Pretreatment of cells with different nitric oxide (NO) donors or atrial natriuretic peptide (ANP) increased endothelial cGMP-content severalfold and blocked H2O2-related effects on permeability; opposite results were obtained with a NO synthase inhibitor. Determination of cGMP degradation in nitroprusside-exposed endothelial cells identified PDE II as the major cGMP metabolizing pathway, whereas PDE III and IV contributed little or nothing. Inhibition of PDE II reduced H2O2-related endothelial hyperpermeability, an effect that could be enhanced synergistically by simultaneous guanylate cyclase activation. In summary, these studies indicate that cGMP-dependent mechanisms (NO donors, ANP, and dibutyryl-cGMP) blocked H2O2-related increases in endothelial permeability. The major cGMP degrading pathway in endothelial cells was PDE II, thereby substituting the missing PDE V in these cells. Simultaneous guanylate cyclase activation and/or PDE II inhibition may be a valuable approach to treat endothelial hyperpermeability.

Animals↗
PubMed1995

Hydrogen peroxide-induced increase in lung endothelial and epithelial permeability--effect of adenylate cyclase stimulation and phosphodiesterase inhibition.

Neutrophil-derived hydrogen peroxide (H2O2) is believed to play an important role in inflammatory lung injury. We investigated the influence of pharmacological agents that increase intracellular c-AMP levels on endothelial and epithelial leakage in response to intravascular H2O2 challenge in buffer-perfused rabbit lungs. Endothelial permeability was assessed by determination of the capillary filtration coefficient (Kfc) and lung weight gain. Measurement of the clearance rate of inhaled aerosolized technetium-99m-labeled diethylenetriamine pentaacetic acid ([99mTc]DTPA) from the lungs into the perfusion fluid was used as an index of alveolar epithelial permeability. Experiments were performed in the presence of acetylsalicylic acid to suppress H2O2-induced lung prostanoid generation and concomitant vasoconstriction. Under these conditions, H2O2 admixture to the perfusate (250 microM) caused a greater than eight-fold increase in Kfc values, resulting in > 30 g lung weight gain within 30 min in the absence of any significant vasopressor response. Pretreatment with the adenylate cyclase activators prostaglandin E1 (0.1 microM) and forskolin (0.1 microM), the dual phosphodiesterase type III/IV inhibitor zardaverine (10 microM) as well as combinations of these drugs all caused a nearly complete suppression of this early Kfc increase; and severe edema formation (> 30 g) was retarded to approximately 50-55 min. In addition to the microvascular leakage response, H2O2 caused a four- to five-fold increase in the [99mTc]DTPA clearance rate, starting within 15 min and culminating after approximately 35 min. Adenylate cyclase activation reduced this epithelial leakage response by approximately 30%, whereas zardaverine exerted no significant effect. We conclude that both microvascular endothelial and alveolar epithelial barrier function are severely compromised by intravascular H2O2 challenge in intact lungs. Pharmacological approaches to increase c-AMP levels, including both adenylate cyclase activation and phosphodiesterase inhibition, partially block the endothelial response and, to a lesser extent, the epithelial response.

Adenylyl Cyclases↗
PubMed1995

Role of endothelial cytoskeleton in high-permeability edema due to botulinum C2 toxin in perfused rabbit lungs.

The cytoskeleton of the endothelial cell has been suggested to regulate endothelial barrier function. We investigated the role of actin in the maintenance of pulmonary capillary integrity in perfused rabbit lungs. As a tool for selective perturbation of actin, we employed Clostridium botulinum C2 toxin, which is composed of a membrane translocation component (C2II) and a component (C2I) effecting ADP-ribosylation of nonmuscle G-actin. ADP-ribosylated actin no longer capable of polymerization but acts as a barbed end-capping protein, thereby effecting selective loss of the nonmuscle F-actin content. In buffer-perfused rabbit lungs, combined application of both toxin components (range 50 pg/ml-5 ng/ml C2I) resulted in a time- and dose-dependent increase in the capillary filtration coefficient (Kfc) with concomitant edema formation. Only 300:600 pg/ml C2I:II sufficed to induce a > 10-fold rise of Kfc values within 110 min. This severe lung permeability increase occurred in the absence of vasomotor responses and potassium release or lactate dehydrogenase release. Application of each single toxin component displayed markedly reduced efficacy. Similar to the C2 toxin effect, severe permeability increase without concomitant hemodynamic changes was evoked by cytochalasin D, known to possess F-actin-disrupting properties. Preloading of lung cells with phallacidin, which in opposition to C2 toxin decreases F-actin depolymerization, significantly reduced the C2 toxin-induced increase in vascular permeability. Electron microscopic examination of C2 toxin-poisoned lungs showed early, extensive endothelial cell attenuations, followed by disruptions of the endothelial layer and marked interstitial edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pore-forming bacterial toxins potently induce release of nitric oxide in porcine endothelial cells.

Nitric oxide (NO) is believed to play an important role in sepsis-related hypotension. We examined the effects of two pore-forming bacterial exotoxins, Escherichia coli hemolysin and Staphylococcus aureus alpha-toxin, on NO formation in cultured porcine pulmonary artery endothelial cells. NO was quantified using a difference-spectrophotometric method based on the rapid and stoichiometric reaction of NO with oxyhemoglobin. Endothelial cyclic guanosine monophosphate levels were also monitored. Both exotoxins increased NO synthesis in endothelial cells in a time- and dose-dependent manner to an extent exceeding that observed with the ionophore A23187 or thrombin. The capacity of exotoxins to induce NO formation may be relevant in patients with severe local or systemic bacterial infections.

Animals↗
PubMed1993

Role of phosphodiesterases in the regulation of endothelial permeability in vitro.

Neutrophil-derived hydrogen peroxide (H2O2) is believed to play an important role in the pathogenesis of vascular injury and pulmonary edema. H2O2 time- and dose-dependently increased the hydraulic conductivity and decreased the selectivity of an endothelial cell monolayer derived from porcine pulmonary arteries. Effects of H2O2 on endothelial permeability were completely inhibited by adenylate cyclase activation with 10(-12) M cholera toxin or 0.1 microM forskolin. 10(-8) M Sp-cAMPS, a cAMP-dependent protein kinase A agonist, was similarly effective. The phosphodiesterase (PDE) inhibitors motapizone (10(-4) M), rolipram (10(-6) M), and zardaverine (10(-8) M), which specifically inhibit PDE-isoenzymes III, IV, and III/IV potently blocked H2O2-induced endothelial permeability when combined with 10(-6) M prostaglandin E1. Overall cellular cAMP content and inhibition of H2O2 effects on endothelial permeability were poorly correlated. H2O2 exposure resulted in a rapid and substantial decrease in endothelial cAMP content. The analysis of the PDE isoenzyme spectrum showed high activities of isoenzymes II, III, and IV in porcine pulmonary endothelial cells. The data suggest that adenylate cyclase activation/PDE inhibition is a powerful approach to block H2O2-induced increase in endothelial permeability. This concept appears especially valuable when endothelial PDE isoenzyme pattern and PDE inhibitor profile are matched optimally.

Animals↗
PubMed1993

Human neutrophil elastase increases permeability of cultured pulmonary endothelial cell monolayers.

Polymorphonuclear leukocytes (PMN) contribute to increased pulmonary vascular permeability in inflammatory lung injury, but the mechanism of their action is complex. In the present study we examined possible effects of PMN-derived proteases on the permeability of pulmonary endothelial cell monolayers grown on polycarbonate filter membranes and exposed continuously to a hydrostatic pressure of 10 cm H2O. Cell- and serum free PMN-supernatants (human PMN, stimulated with 30 ng/ml phorbol-myristate acetate for 30 min, presence of catalase, were centrifuged, the supernatants were passed through a 0.45 micron filter) dose-dependently (calculated PMN: endothelial cell ratio of 2:1 and more) increased hydraulic conductivity of endothelial cell monolayers ten- to twentyfold within 20-70 min. At the same time the dextran reflection coefficient decreased from 0.8 to 0.1. Phase contrast and scanning electronmicroscopy showed a widening of intercellular gaps. The effects of the postsecretory PMN-supernatant were blocked dose-dependently by inhibitors of human neutrophil elastase (HNE) but not of cathepsin G. On quantitative grounds highly purified HNE was similarly active as postsecretory PMN supernatant. The effects of HNE were inhibited by pretreatment with eglin-c or heat, but not with heparin. The data suggest that HNE is an effective and sufficient neutrophil-derived mediator to increase endothelial permeability. HNE appears to act primarily enzymatically and not as a cationic protein.

Amino Acid Sequence↗
PubMed1993

[Three cases of a fulminant course of idiopathic pulmonary fibrosis (Hamman-Rich syndrome)].

The Hamman-Rich syndrome is defined as an acute pulmonary disease of unclear aetiology that takes a rapid and prognostically unfavourable, usually fatal course. We report on three patients admitted to the intensive-care ward during a period of 6 months in a state of mandatory artificial respiration, each patient dying within 3 weeks after admission. Basing on clinical and histological criteria these patients were diagnosed as suffering from Hamman-Rich syndrome. At the time of the clinically identifiable onset of the disease all the patients had fever (> 39 X), leucocytosis (> 20 x 10(3)/microliters) and dyspnoea. These signs and symptoms were at first, in conjunction with the radiological identification of diffuse pulmonary infiltrations, misdiagnosed as pneumonia. The patients had to be artificially respirated after a short time because of the foundroyant course of the disease. Despite optimised respiratory parameters it was already initially apparent that there was a severe disturbance of the gas exchange function (paO2/FiO2 < 150) and high respiratory pressures (> 40 mmHg). Polymorphonuclear neutrophilics dominated in the bronchoalveolar lavage. Lung biopsy showed marked fibrosing that was a decisive factor in diagnosing. An infectious agent as triggering cause of the disease could not be identified in any of the patients. Treatment was effected with antibiotics, steroids and cyclophosphamide. The patients died after 14, 17 and 21 days, respectively, from intractable respiratory insufficiency with increasing loss of compliance of the lungs (compliance of lungs and thorax < 20 ml/mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Stimulation of PAF-synthesis in pulmonary artery endothelial cells by Staphylococcus aureus alpha-toxin.

Staphylococcus aureus alpha-toxin is a pore-forming exotoxin that probably represents a significant virulence factor in staphylococcal infections. Previous studies demonstrated that this agent stimulated arachidonate metabolism with subsequent formation of prostacyclin in endothelial cells and leukotriene B4 in granulocytes. We now examined the effect of alpha-toxin on the synthesis of platelet-activating factor (PAF) in cultured porcine pulmonary artery endothelial cells. PAF was labeled by bioincorporation of tritiated acetate and separated/quantitated using thin-layer chromatography, straight-phase-HPLC, or post-HPLC-bioassay. Alpha-toxin induced synthesis of small amounts of PAF in a time- and dose-dependent manner. The maximal amount of PAF elicited by alpha-toxin was approximately 7% of that observed after application of the ionophore A23187. Staphylococcal alpha-toxin but not the ionophore induced a rapid fall in cellular ATP-content. On kinetic grounds, the decrease in ATP-levels did not explain the differences in stimulated PAF-synthesis. Low amounts of PAF induced by the action of alpha-toxin on endothelial cells may contribute to the development of inflammatory lesions in infectious disease.

Adenosine Triphosphate↗