Pulmonary haemorrhage in a patient with idiopathic membranous nephropathy.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗
Biomedical subjects
C J Wiedermann
Publications and source records attributed to C J Wiedermann.
The chemotaxis of human peripheral blood B lymphocytes by beta-endorphin is reversible by naloxone.
Explore the source record for details and available documents.
B-Lymphocytes↗
Decreased levels of beta-endorphin in circulating mononuclear leukocytes from patients with acute myocardial infarction.
Lymphocytes can be activated to produce and release opioid peptides. We investigated the levels of immunoreactive beta-endorphin in peripheral blood mononuclear cells from 11 patients with acute myocardial infarction. The concentrations of beta-endorphin in mononuclear leukocytes of 30.2 +/- 6.9 pg/10(6) cells on admission were in the normal range of 20-40 pg/10(6) cells and decreased significantly to 6.9 +/- 1.9 pg/10(6) cells after 48 h (p < 0.05). Decreased levels of mononuclear leukocyte-associated beta-endorphin in acute myocardial infarction may be due to the release of endogenous opioid after stimulation by stress and acute-phase reactants and play a role in inflammation and pain.
C-Reactive Protein↗
Human and bovine endothelial cell monolayers are differentially activated for neutrophil transmigration by human plasma.
Endothelial cells used in transendothelial migration assays have been derived from different sources including human umbilical vein and bovine pulmonary artery. As plasma-induced activation of endothelial cells for enhanced transmigration of leukocytes may be pathophysiologically relevant, the role of species differences between plasma and endothelial cells was studied. The effects of human plasma on human umbilical vein and bovine pulmonary artery endothelial cells with regard to transmigration of neutrophils were compared. Transendothelial migration of neutrophils was tested employing endothelial cell-covered Transwell cell culture chamber inserts with micropore filters of 5 microns pore size. Results showed that human plasma induces neutrophil transmigration of both human umbilical vein and bovine pulmonary artery endothelial cell monolayers. Plasma samples from 50 to 69 year old men with and without carotid arteriosclerosis (N = 152) stimulated endothelial cells of human origin significantly stronger for transmigration of neutrophils than endothelial cells of bovine origin. Analyses of limits of agreement and of correlation of the two methods indicated that bovine pulmonary artery and human umbilical vein endothelial cells cannot replace each other in assays of plasma-induced activation of transmigration. Plasma levels of soluble adhesion molecule P-selectin, which are elevated in patients with arteriosclerotic diseases, are inversely related to plasma-induced activation of neutrophil transmigration of endothelial monolayers of human origin but not of bovine origin (N = 65). As rates of transmigration that were induced by plasma from subjects without carotid arteriosclerosis (N = 73) were significantly related between human and bovine endothelium, elevated plasma levels of soluble P-selectin may thus affect results of assays for plasma-induced activation of neutrophil transmigration of endothelial monolayers in a species-specific manner.
Adult↗
Pentoxifylline differentially regulates migration and respiratory burst activity of the neutrophil.
TNF is produced by monocytes/macrophages in response to endotoxin, which may lead to septic shock. TNF stimulates neutrophil adherence, degranulation, and superoxide production, but inhibits neutrophil migration. A mitigating anti-inflammatory effect can be experimentally induced in septic shock by TNF blockers, such as pentoxifylline, and is also suggested for treatment with hrG-CSF. With regard to the combination of pentoxifylline and hrG-CSF, the purpose of this investigation was to explore whether and in what way the effects of hrG-CSF and pentoxifylline interact with each other in neutrophils. To this end, we studied the effects of pentoxifylline on TNF- and G-CSF-induced modulation of neutrophil chemotaxis and O2 release. TNF and G-CSF decreased directed migration of neutrophils to FMLP or IL-8. High-dose pentoxifylline (1 mM) was able to counteract the effect of TNF but not that of G-CSF on neutrophil migration. In the presence of pentoxifylline, TNF and G-CSF were unable to stimulate respiratory burst. In contrast, pre-exposure of cells to pentoxifylline followed by washing increased the priming effect of TNF or hrG-CSF on neutrophil respiratory burst activity. The methylxanthine derivative by itself showed no effect on spontaneous and fMLP-stimulated O2 release by neutrophils. Stimulation of neutrophil respiratory burst by pentoxifylline may not be detectable in the presence of pentoxifylline due to its known oxygen-radical scavenging function. Results suggest that by blocking the inflammatory action of TNF on neutrophils, pentoxifylline may diminish endothelial cell damage caused by inhibited neutrophil chemotaxis. On the other hand, since transiently present pentoxifylline may enhance the respiratory burst activity of TNF- or hrG-CSF-primed neutrophils, concomitant administration of pentoxifylline and hrG-CSF to patients with SIRS/sepsis might diminish beneficial effects of the latter and additional deleterious effects might occur.
Chemotaxis, Leukocyte↗
Plasma levels of troponin T after electrical cardioversion of atrial fibrillation and flutter.
To establish possible myocardial damage by direct-current countershock, we measured plasma levels of troponin T after electrical cardioversion in 33 nonselected patients with atrial fibrillation or flutter. Unchanged normal levels of troponin T indicate that significant myocardial cell injury by shocks in the usual dosage is unlikely to occur.
Adult↗
Differential chemotactic activities of sensory neuropeptides for human peripheral blood mononuclear cells.
We studied the chemotactic effects of calcitonin gene-related peptide, vasoactive intestinal peptide, substance P (SP), and secretoneurin on PBMC and PBL using micropore filter assays. All four peptides induced migration of PBMC, whereas only calcitonin gene-related peptide, vasoactive intestinal peptide, and SP were chemotactic for PBL. Secretoneurin, known to induce monocyte chemotaxis, was unable to affect lymphocyte migration. Effects of SP on PBL were characterized by checkerboard analyses and represented true chemotaxis. Both T and B cells responded chemotactically to SP, the functional activity of SP residing in its C-terminal amino acid sequence. Involvement of neurokinin (NK) receptors was supported by inhibition of SP-induced migration of PBL with an NK1 receptor antagonist and induction of migration with [Sar9, Met(O2)11]SP and [PyrGlu6, Pro9]SP(6-11), two specific agonists for NK1 receptors, but not with [beta-Ala8]NK A(4-10), an agonist for NK2 receptors. PBL chemotaxis to SP was abolished by inhibition of tyrosin kinase but not by that of protein kinase C. Preincubation of PBL with pertussis or cholera toxin inhibited SP chemotaxis, indicating that in PBL, NK receptors for chemotaxis probably are coupled with G protein and involve a tyrosin kinase signaling pathway. We conclude that, together with calcitonin gene-related peptide and vasoactive intestinal peptide, SP is a lymphocyte chemoattractant, whereas secretoneurin, which is coreleased from sensory nerve endings, is not.
Cells, Cultured↗
Effects of thalidomide on neutrophil respiratory burst, chemotaxis, and transmigration of cytokine- and endotoxin-activated endothelium.
Vascular endothelium activated by endotoxin and cytokines plays an important role in organ inflammation and blood leukocyte recruitment. Neutrophils, which are a homogeneous population of effector cells, are rapidly attracted in large numbers to sites of inflammation where they form an early response to infection or injury. Excessive production of various interleukins, TNF, arachidonic acid metabolites, and other substances by neutrophils and macrophages results in systemic endothelial cell injury, a fundamental problem. In the present study, we investigated in vitro the effects of thalidomide (THD) on activation of endothelial cells for enhanced transmigration of neutrophils by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF), and interleukin-1 (IL-1). Modulation of endotoxin- and cytokine-induced neutrophil chemotaxis and respiratory burst by THD were also studied. Treatment of HUVEC with THD in combination with LPS, TNF, and IL-1, respectively, antagonized LPS-activated transmigration of neutrophils but stimulated the effects of TNF and IL-1. All of the agents used-THD, LPS, TNF, and IL-1-inhibited neutrophil chemotaxis. Addition of THD to the neutrophils had no effect on LPS-inhibited chemotaxis whereas the TNF- and IL-1-induced chemotaxis was modulated in a bimodal manner. However, THD failed to influence neutrophil respiratory burst activity. Results demonstrate that THD differentially affects mediator-induced activation of HUVEC and neutrophils.
Cells, Cultured↗
Interleukin-8-induced human peripheral blood B-lymphocyte chemotaxis in vitro.
We studied chemotactic effects of interleukin-8 (IL-8) on human peripheral blood lymphocytes (PBL) using micropore filter assays. As identification of chemotactic responses depends on the status of activation of cells, magnetic cell sorting (MACS) was performed providing freshly isolated B-lymphocytes of highest purity. B-lymphocytes responded chemotactically to IL-8 in a dose-dependent manner. We conclude that IL-8 may play a role in both T- and B-lymphocyte trafficking by acting directly on the cells.
B-Lymphocytes↗
Augmentation of tumor necrosis factor-alpha-induced priming of fMet-Leu-Phe-stimulated neutrophils by pentoxifylline.
Tumor necrosis factor-alpha (TNF) is reported to cause tissue damage via enhanced neutrophil (PMNL) degranulation, superoxide production and altered PMNL migration. We investigated the effect of pentoxifylline (PTX) on TNF-induced respiratory burst activity of the PMNL. Since PTX has been reported to influence TNF-induced PMNL functions, our studies focused on the effects of timing and duration of the presence of PTX on superoxide anion production by PMNL exposed to TNF. When PMNL are exposed to PTX prior to priming with TNF and triggering with fMLP, respiratory burst activity was significantly enhanced by PTX, whereas the stimulatory effect of TNF was completely blunted by the continuous presence of PTX. Since free radical-scavenging properties of PTX have only recently been identified and may explain inhibitory effects on TNF-induced respiratory burst reported in the literature, our data for the first time suggests additive priming actions of PTX and TNF on PMNL respiratory burst activity.
Chemotaxis, Leukocyte↗
Staurosporine-dependent activation of human endothelial cell monolayers for neutrophil adherence by secretoneurin.
Functions of secretoneurin include chemotaxis for monocytes and endothelial cells, and inhibition of endothelial cell proliferation. Inhibition of monocyte chemotaxis by staurosporine indicated involvement of specific signaling mechanisms. We have tested effects of kinase inhibitors on activation of endothelial cells for neutrophil adherence by secretoneurin. Pretreatment of endothelial cells by secretoneurin induced in endothelium increased adhesiveness to neutrophils. Addition of staurosporine, an inhibitor of protein kinase C, completely abolished endothelial cell activation, whereas tyrphostin-23, a tyrosin kinase inhibitor, had no effect. Results on activation of neutrophil-endothelial cell adherence by secretoneurin demonstrate that specific signaling mechanisms are involved in endothelial cell activation.
Cell Adhesion↗
Response of vascular smooth muscle cells to the neuropeptide secretoneurin. A functional role for migration and proliferation in vitro.
Mesenchymal cell migration and replication are central biologic events involved in atherosclerosis and lung and hepatic fibrosis. Tissue repair and fibrosis are thought to be regulated by growth regulatory molecules, comprising both stimulators and inhibitors of mesenchymal cell functions, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), fibroblast growth factors, and several neuropeptides such as substance P. Secretoneurin (SN), a novel 33-amino acid neuropeptide derived from secretogranin II (chromogranin C), is widely distributed in the central and peripheral nervous and neuroendocrine systems, including afferent C-fibers, and can be released in the periphery by capsaicin. Recently, we reported that SN triggers the selective migration of human monocytes and fibroblasts in vitro, implicating its involvement in inflammatory responses. We report herein that SN stimulates specific migration (maximal response at 10(-10) M) of cultured arterial smooth muscle cells (SMCs), originating from rat thoracic aorta, and initiates DNA synthesis and SMC growth (BrdU incorporation, MTT test) with a maximum at 10(-8) M SN to a similar extent as observed by PDGF. Both functional activities of SN were inhibited by specific anti-SN immunoglobulins (dilution, 1:1000), and furthermore, a trypsinized SN peptide (10(-8) M) was unable to provoke biologic effects. Our studies suggest that SN functions as a regulatory peptide to modulate SMC migration and proliferation, which in conjunction with other factors could serve to aggravate and accelerate the development of atherosclerotic or restenotic lesions at sites of vascular injury.
Animals↗
Inhibition of proliferation and stimulation of migration of endothelial cells by secretoneurin in vitro.
Vascular cell responses in inflammation are affected by several neuropeptides of perivascular nerve fibers. Secretoneurin is a 33-amino acid peptide that is coreleased from these nerve endings with other proinflammatory neuropeptides, eg, substance P and calcitonin gene-related peptide. Furthermore, secretoneurin has been shown to be chemotactic for human skin fibroblasts and human blood monocytes in vitro and in vivo. An action on cellular components of the vascular wall is not yet reported. We therefore investigated in vitro effects of this novel sensory neuropeptide on endothelial cells. Secretoneurin exerted a potent and reversible inhibitory effect both on endothelial cell growth under low serum conditions (1% fetal calf serum) and endothelial cell growth factor-activated endothelial cell proliferation. We show in the present study that secretoneurin exerts this effect on aortic (rat) and pulmonary artery (bovine) endothelial cells, as well as venous (human umbilical vein) endothelium. Endothelial cell chemotaxis was tested by means of three different migration assays employing nitrocellulose and polycarbonate micropore filters. Secretoneurin consistently exhibited potent chemoattractant activity. The effective concentrations for the observed effects were in the picomolar range. The combination of chemotactic and antiproliferative effects on endothelial cells suggests that secretoneurin may act as a regulatory factor of vascular cell functions.
Animals↗
Mevalonate-dependent inhibition of transendothelial migration and chemotaxis of human peripheral blood neutrophils by pravastatin.
Pravastatin, a hydrophilic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, has been reported to beneficially affect atherogenesis, plaque stability, and transient myocardial ischemia in significant coronary artery disease by influencing lipid metabolism and by intracellular signaling via mevalonate pathway products other than cholesterol. Leukocytes are implicated to play a pathophysiological role in these events. We were interested in finding out whether pravastatin could affect transendothelial migration (TEM), chemotaxis, and respiratory burst activity of the neutrophil ex vivo. In addition, effects on monocyte and T-lymphocyte chemotaxis were tested. For TEM assays, monolayers of human umbilical vein endothelial cells (HUVECs) were grown to confluence on polycarbonate filters bearing 5-microns pores in Transwell (Costar) culture plate inserts. Chemotaxis experiments were performed using modified Boyden chambers with cellulose nitrate micropore filters. Respiratory burst activity was measured fluorometrically. Treatment of neutrophils and monocytes with pravastatin at 2 to 200 mumol/L and 10 to 1000 mumol/L, respectively, significantly decreased chemotaxis triggered by fMet-Leu-Phe. This effect was abolished in the presence of mevalonic acid (500 mumol/L); no effect of pravastatin was seen on T-lymphocyte chemotaxis triggered by interleukin-8. Preincubation of neutrophils with pravastatin (200 mumol/L) also resulted in a significant reduction in the number of neutrophils that transmigrated a tumor necrosis factor-stimulated or lipopolysaccharide-stimulated HUVEC monolayer. At none of the concentrations tested (2 pmol/L to 200 mumol/L) did pravastatin affect neutrophil respiratory burst activity. We conclude that pravastatin may alter monocyte chemotaxis and neutrophil-endothelial interactions in migratory responses at concentrations obtained in vivo with cholesterol-lowering doses.
Cell Movement↗
Secretoneurin-induced in vitro chemotaxis of human monocytes is inhibited by pertussis toxin and an inhibitor of protein kinase C.
The sensory neuropeptide secretoneurin (SN) triggers chemotactic migration of monocytes. We have investigated the possibility that SN, like other chemoattractants such as formyl-Met-Leu-Phe and chemokines, might stimulate migration of monocytes by G protein and protein kinase C (PKC) activation and induce Ca2+i release. We report that preincubation of monocytes with pertussis toxin inhibited SN chemotaxis. Staurosporine, an inhibitor of PKC, significantly decreased SN-induced chemotaxis of monocytes, suggesting that PKC may be involved in the signaling. Tyrphostin-23, which inhibits tyrosin kinase, did not affect SN-induced chemotaxis of monocytes. This suggests that SN uses a signaling mechanism that is coupled to pertussis toxin-sensitive G proteins. Involvement of phospholipase C beta as a result of PKC activation is suggested by a SN-induced increase of intracellular Ca2+ concentration in monocytes.
Aniline Compounds↗
Deactivation of chemotaxis of human neutrophils by priming with secretogranin II-derived secretoneurin.
Secretoneurin (SN), a novel neuropeptide, specifically induces the selective chemotactic migration of monocytes in vitro and in vivo. Mediation of the migratory effects by yet unidentified receptors for secretoneurin is likely. Whether phagocytes other than monocytes are targets of SN's action, is currently unknown. Since previous data suggested that SN does not induce chemotaxis of neutrophils, we tested SN priming for respiratory burst activity, adherence to endothelial cell (EC) monolayers and effects on chemoattractant-stimulated migration of neutrophils. We found that priming of neutrophils with SN fails to enhance triggered respiratory burst activity or adherence to EC as compared to tumor necrosis factor-alpha (TNF), a well-known neutrophil-priming cytokine. Pretreatment, however, revealed an increase in spontaneous locomotion, and significant antagonism of formylpeptide (FMLP)-stimulated migration of neutrophils in modified Boyden chamber assays. The latter effect was similar to inhibition of FMLP-stimulated chemotaxis by TNF. The effects of SN on neutrophil migration could be abolished by an antiserum to SN, indicating its specificity. Data show that in vitro neutrophils are specifically affected by SN possibly by activation of a priming-type receptor. Since neutrophils represent a valuable tool for receptor research, further studies on SN receptors of leukocytes may be performed on these cells.
Animals↗
Stimulation of human skin fibroblast migration by the neuropeptide secretoneurin.
Fibroblasts, besides other cells, are called upon when tissue sustains an immunological, mechanical or chemical injury. Fibroblasts migrate into the site of inflammation, proliferate and synthesize and remodel a new matrix. These cellular responses are mediated locally by the release of neuropeptides from sensory nerve endings. Secretoneurin is a newly discovered 33-amino acid neuropeptide derived from secretogranin II (chromogranin C), which is found in sensory afferent C-fibers. We show here that secretoneurin triggers the selective migration of human skin fibroblasts in vitro, but does not stimulate their proliferation. The attraction of human skin fibroblasts toward secretoneurin could be blocked by specific anti-secretoneurin antibodies and is mediated by the C-terminal fragment of the peptide. The observed activity of this sensory neuropeptide is the first description of a specific effect on human skin fibroblasts and suggests a role for secretoneurin in inflammation and wound healing.
Antibodies↗
Induction of endothelial cell differentiation into capillary-like structures by substance P.
Angiogenesis is an important process in inflammatory diseases and wound healing. We observed that the proinflammatory neuropeptide, substance P, stimulated angiogenesis in an in vitro model using human umbilical cord vein endothelial cells cultured on a basement membrane (Matrigel) substrate. Substance P stimulated endothelial cell differentiation into capillary-like structures in a dose-dependent manner. Stimulation of endothelial cell differentiation is a newly recognized biological function of substance P. The increased levels of substance P found in chronic inflammatory conditions may play an important role in tissue repair by promoting the development of new vessels and thus achieving compensation for ischemia.
Basement Membrane↗