scholarly journals Lipoxin A4 induces hyperadhesiveness in human endothelial cells for neutrophils

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 948-953
Author(s):  
R Lerner ◽  
M Heimburger ◽  
J Palmblad
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Cytosolic Calcium ◽  
Leukotriene B4 ◽  
Polymorphonuclear Neutrophil ◽  
Maximal Response ◽  
Neutrophil Granulocytes ◽  
Lipoxin A4

Lipoxin A4 (LXA4), but not lipoxin B4, induced in vitro a dose- dependent, slowly emerging hyperadhesiveness in human umbilical vein endothelial cells (HUVEC), leading to a 1.9-fold increase in the binding of neutrophils (polymorphonuclear neutrophil granulocytes [PMN]). The maximal response to LXA4 occurred at 1 nmol/L and after 30 minutes of treatment of HUVEC. These response kinetics were intermediate in comparison with those of fast-acting inducers of HUVEC adhesivity (eg, thrombin, leukotriene B4 [LTB4] or platelet activating factor [PAF]), needing 5 to 15 minutes, or to the slow inducer interleukin-1 (IL-1 beta), which requires hours. The maximal LXA4 effect was slightly lower than that of LTB4 (100 nmol/L) and thrombin (1 U/mL), and less than that of PAF (100 nmol/L) or IL-1 beta (2.5 U/mL) (2.2-, 2.0-, 2.4-, or 13.6-fold increases, respectively). The LXA4 effect was inhibited by the PAF receptor antagonist WEB-2086; however, it could not be blocked by pertussis toxin. LXA4 conferred a slow, sustained increase in HUVEC cytosolic calcium ion concentrations, whereas thrombin did so rapidly and transiently. LXA4 also caused PMN to become hyperadhesive. Thus, this novel effect of LXA4 on HUVEC appears to be associated with endogenous PAF expression and slow increases of cytosolic calcium concentrations but not pertussis- sensitive G proteins.

scholarly journals Lipoxin A4 induces hyperadhesiveness in human endothelial cells for neutrophils

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 948-953 ◽  
Author(s):  
R Lerner ◽  
M Heimburger ◽  
J Palmblad
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Cytosolic Calcium ◽  
Leukotriene B4 ◽  
Polymorphonuclear Neutrophil ◽  
Maximal Response ◽  
Neutrophil Granulocytes ◽  
Lipoxin A4

Abstract Lipoxin A4 (LXA4), but not lipoxin B4, induced in vitro a dose- dependent, slowly emerging hyperadhesiveness in human umbilical vein endothelial cells (HUVEC), leading to a 1.9-fold increase in the binding of neutrophils (polymorphonuclear neutrophil granulocytes [PMN]). The maximal response to LXA4 occurred at 1 nmol/L and after 30 minutes of treatment of HUVEC. These response kinetics were intermediate in comparison with those of fast-acting inducers of HUVEC adhesivity (eg, thrombin, leukotriene B4 [LTB4] or platelet activating factor [PAF]), needing 5 to 15 minutes, or to the slow inducer interleukin-1 (IL-1 beta), which requires hours. The maximal LXA4 effect was slightly lower than that of LTB4 (100 nmol/L) and thrombin (1 U/mL), and less than that of PAF (100 nmol/L) or IL-1 beta (2.5 U/mL) (2.2-, 2.0-, 2.4-, or 13.6-fold increases, respectively). The LXA4 effect was inhibited by the PAF receptor antagonist WEB-2086; however, it could not be blocked by pertussis toxin. LXA4 conferred a slow, sustained increase in HUVEC cytosolic calcium ion concentrations, whereas thrombin did so rapidly and transiently. LXA4 also caused PMN to become hyperadhesive. Thus, this novel effect of LXA4 on HUVEC appears to be associated with endogenous PAF expression and slow increases of cytosolic calcium concentrations but not pertussis- sensitive G proteins.

Leukotrienes stimulate neutrophil adhesion to mesangial cells: modulation with lipoxins

1990 ◽  
Vol 259 (5) ◽  
pp. F809-F815 ◽  
Author(s):  
H. R. Brady ◽  
U. Persson ◽  
B. J. Ballermann ◽  
B. M. Brenner ◽  
C. N. Serhan
Keyword(s):  
High Performance ◽  
Mesangial Cells ◽  
Divalent Cations ◽  
Leukotriene B4 ◽  
Polymorphonuclear Neutrophil ◽  
Induced Response ◽  
Lipoxin A4 ◽  
Leukotriene D4 ◽  
Adhesion Process

We have examined polymorphonuclear neutrophil (PMN) adhesion to mesangial cells (MC) in vitro and have assessed the actions of lipoxygenase (LO) products in this process. On exposure to either leukotriene B4 (LTB4), or leukotriene D4 (LTD4), 111In-labeled PMNs adhere to monolayers of cultured MC. These actions were rapid in onset (less than 5 min) and dependent upon leukotriene concentration (10(-9) to 10(-6) M) and the presence of divalent cations. Adhesion was sustained (0-30 min), and neither LTB4 nor LTD4 was metabolized to inactive products during PMN-MC interaction, as determined by their recovery after reverse-phase high-performance liquid chromatography. LTB4 was a PMN-directed stimulus, whereas LTD4 appeared to act on MC. A monoclonal antibody (TS 1/18) against the CD18 component of the PMN CD18/CD11 adhesion complex inhibited the LTB4-induced response, indicating involvement of this PMN glycoprotein in the adhesion process. In contrast, this antibody did not affect LTD4-induced adhesion, suggesting that this response was mediated by other adhesion epitopes. When added alone, neither lipoxin A4 (LXA4) nor lipoxin B4 (LXB4) provoked PMN adhesion to MC. In contrast, LXA4 and LXB4 at equimolar concentrations attenuated the LTD4- but not LTB4-induced response. Together, these results provide further evidence that LO-derived eicosanoids may constitute important early signals that regulate PMN-MC interaction in glomerular inflammation.

Leukotriene B4-induced neutrophil-mediated endothelial leakage in vitro and in vivo

1991 ◽  
Vol 71 (4) ◽  
pp. 1322-1330 ◽  
Author(s):  
S. Rosengren ◽  
A. M. Olofsson ◽  
U. H. von Andrian ◽  
E. Lundgren-Akerlund ◽  
K. E. Arfors
Keyword(s):  
Umbilical Vein ◽  
Neutrophil Migration ◽  
Fluorescein Isothiocyanate ◽  
Leukotriene B4 ◽  
Vascular Leakage ◽  
Neutrophil Granulocytes ◽  
Vitro Assay ◽  
Umbilical Vein Endothelial Cells

The vascular leakage of macromolecules seen in several models after application of leukotriene B4 (LTB4) is mediated by neutrophil granulocytes. We describe here an in vitro assay for this event. Human umbilical vein endothelial cells were grown on polycarbonate filters separating luminal and abluminal compartments of fluid. Both clearance rate of fluorescein isothiocyanate albumin and neutrophil migration through the endothelial monolayer were increased when LTB4 (10–100 nM) was added to the abluminal compartment. However, if LTB4 was instead added to the luminal compartments together with the neutrophils, no migration or change in clearance could be detected. These findings were confirmed in vivo in the cheek pouches of anesthetized hamsters, where extravascular application of LTB4 induced intravascular adhesion of neutrophils, accompanied by neutrophil-dependent vascular leakage. On the other hand, intravascular deposition of LTB4 with micropipettes induced adhesion of leukocytes but no leakage. In conclusion, the presence of neutrophils adhering to endothelium does not necessarily imply the development of neutrophil-mediated vascular leakage. Instead, the leakage appears connected to the process of neutrophil chemotaxis.

scholarly journals Borrelia burgdorferi and Interleukin-1 Promote the Transendothelial Migration of Monocytes In Vitro by Different Mechanisms

1998 ◽  
Vol 66 (10) ◽  
pp. 4875-4883 ◽  
Author(s):  
Margaret J. Burns ◽  
Martha B. Furie
Keyword(s):  
Endothelial Cells ◽  
T Lymphocytes ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Neutralizing Antibodies ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Transendothelial Migration ◽  
Mononuclear Leukocytes

ABSTRACT A prominent feature of Lyme disease is the perivascular accumulation of mononuclear leukocytes. Incubation of human umbilical vein endothelial cells (HUVEC) cultured on amniotic tissue with either interleukin-1 (IL-1) or Borrelia burgdorferi, the spirochetal agent of Lyme disease, increased the rate at which human monocytes migrated across the endothelial monolayers. Very late antigen 4 (VLA-4) and CD11/CD18 integrins mediated migration of monocytes across HUVEC exposed to either B. burgdorferi or IL-1 in similar manners. Neutralizing antibodies to the chemokine monocyte chemoattractant protein 1 (MCP-1) inhibited the migration of monocytes across unstimulated, IL-1-treated, or B. burgdorferi-stimulated HUVEC by 91% ± 3%, 65% ± 2%, or 25% ± 22%, respectively. Stimulation of HUVEC with B. burgdorferi also promoted a 6-fold ± 2-fold increase in the migration of human CD4+ T lymphocytes. Although MCP-1 played only a limited role in the migration of monocytes acrossB. burgdorferi-treated HUVEC, migration of CD4+T lymphocytes across HUVEC exposed to spirochetes was highly dependent on this chemokine. The anti-inflammatory cytokine IL-10 reduced both migration of monocytes and endothelial production of MCP-1 in response to B. burgdorferi by approximately 50%, yet IL-10 inhibited neither migration nor secretion of MCP-1 when HUVEC were stimulated with IL-1. Our results suggest that activation of endothelium by B. burgdorferi may contribute to formation of the chronic inflammatory infiltrates associated with Lyme disease. The transendothelial migration of monocytes that is induced by B. burgdorferi is significantly less dependent on MCP-1 than is migration induced by IL-1. Selective inhibition by IL-10 further indicates that B. burgdorferi and IL-1 employ distinct mechanisms to activate endothelial cells.

scholarly journals In vitro biosynthesis of leukemia inhibitory factor/human interleukin for DA cells by human endothelial cells: differential regulation by interleukin-1 alpha and glucocorticoids

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3763-3770 ◽  
Author(s):  
C Grosset ◽  
B Jazwiec ◽  
JL Taupin ◽  
H Liu ◽  
S Richard ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Leukemia Inhibitory Factor ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Suppressive Effect ◽  
Inhibitory Factor ◽  
Basal Secretion ◽  
In Vitro Biosynthesis

Endothelial cell (EC) may represent a major source of cytokines in the bone marrow. In this study we have examined the production and the regulation of the production of leukemia inhibitory factor/human interleukin for DA cells (LIF/HILDA) by EC. Human umbilical vein endothelial cells (HUVEC) were chosen as a working model as they are a well known source of cytokines. These cells secrete LIF/HILDA (90 pg/mL/10(6) cells/48 h) in basal conditions. This secretion is profoundly altered by interleukin-1 alpha (IL-1 alpha). Secretion of LIF/HILDA is increased threefold on stimulation with IL-1 alpha at a concentration of 100 IU/mL. The secreted protein is bioactive as demonstrated by its proliferative effects on DA1a cells. Modulation of the production of LIF/HILDA by glucocorticoids (GC) was also examined. In striking contrast to what was observed for IL-1 alpha, the synthetic GC dexamethasone (DXM) at a concentration of 10(-6) mol/L consistently inhibited the basal secretion of LIF/HILDA by an average of threefold and suppressed the IL-1 alpha-induced increase of the secretion of this cytokine by HUVEC. In an effort to extend results obtained with HUVEC to the bone marrow endothelium, we have also examined the production of LIF/HILDA by human bone marrow endothelial cells (HBMEC). Our study shows that HBMEC are quantitatively a very important source of this cytokine (above 7.25 ng/mL/10(6) cells/48 h) suggesting that they are a major source of LIF/HILDA in the bone marrow. Again, IL-1 alpha proved to be a very potent stimulus for the secretion of LIF/HILDA and synthetic GC such as DXM when used at a concentration of 10(-6) mol/L inhibited by an average of threefold the basal secretion of LIF/HILDA and had suppressive effect on the IL-1 alpha-induced increase of this secretion. The downregulation of LIF/HILDA production in the bone marrow by GC may be important to understand the effects of GC on hematopoiesis.

scholarly journals Platelet-derived interleukin 1 induces human endothelial adhesion molecule expression and cytokine production.

1991 ◽  
Vol 174 (4) ◽  
pp. 785-790 ◽  
Author(s):  
C M Hawrylowicz ◽  
G L Howells ◽  
M Feldmann
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Saphenous Vein ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Human Umbilical Cord ◽  
Intercellular Adhesion Molecule 1 ◽  
Activated Platelets

Interleukin 1 (IL-1) plays a central role in the regulation of the body's response to infectious and inflammatory stimuli. Recent evidence has shown that human platelets express a cell associated form of this proinflammatory cytokine very rapidly following activation. Since one of the earliest events in inflammation is frequently the rapid adhesion of platelets to injured endothelium, it was of interest to determine whether platelets express IL-1 in a functionally relevant form that can alter the phenotype of human endothelial cells in vitro. Thrombin activated platelets induced significant expression of the adhesion molecule intercellular adhesion molecule 1, as well as secretion of the IL-1 inducible cytokines IL-6 and granulocyte macrophage colony stimulating factor by cultured human umbilical cord and saphenous vein endothelial cells. This was inhibited by prior treatment of the platelets with antibody specific for IL-1. These results suggest that platelet delivered IL-1 might initiate and regulate some of the earliest phases of the inflammatory response. An additional observation of interest was differential induction of endothelial leucocyte adhesion molecule 1 by activated platelets on saphenous vein but not umbilical vein but not umbilical vein endothelial cells, which suggests functional heterogeneity of the endothelial cells.

scholarly journals Endothelium-derived GM-CSF influences expression of oncostatin M

2011 ◽  
Vol 301 (4) ◽  
pp. C947-C953 ◽  
Author(s):  
Wafa M. Elbjeirami ◽  
Elizabeth M. Donnachie ◽  
Alan R. Burns ◽  
C. Wayne Smith
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Neutralizing Antibody ◽  
Transendothelial Migration ◽  
Oncostatin M ◽  
Polymorphonuclear Neutrophil ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Gm Csf

During and after transendothelial migration, neutrophils undergo a number of phenotypic changes resulting from encounters with endothelium-derived factors. This report uses an in vitro model with human umbilical vein endothelial cells and isolated human neutrophils to examine the effects of two locally derived cytokines, granulocyte (G)-macrophage (M) colony-stimulating factor (GM-CSF) and G-CSF, on oncostatin M (OSM) expression. Neutrophils contacting activated HUVEC expressed and released increased amounts of oncostatin M (OSM), a proinflammatory cytokine known to induce polymorphonuclear neutrophil adhesion and chemotaxis. Neutrophil transendothelial migration resulted in threefold higher OSM expression and protein levels compared with nontransmigrated cells. Addition of anti-GM-CSF neutralizing antibody reduced OSM expression level but anti-G-CSF was without effect. GM-CSF but not G-CSF protein addition to cultures of isolated neutrophils resulted in a significant increase in OSM protein secretion. However, inhibition of β2integrins by neutralizing antibody significantly reduced GM-CSF-induced OSM production indicating this phenomenon is adhesion dependent. Thus cytokine-stimulated endothelial cells can produce sufficient quantities of GM-CSF to influence in an adhesion-dependent manner, the phenotypic characteristics of neutrophils resulting in the latter's transmigration. Both transmigration and adhesion phenomenon lead to increased production of OSM by neutrophils that then play a major role in inflammatory response.

Perturbation of Platelet Adhesion to Endothelial Cells by Plasminogen Activation In Vitro

1997 ◽  
Vol 78 (02) ◽  
pp. 934-938 ◽  
Author(s):  
Hsiun-ing Chen ◽  
Yueh-I Wu ◽  
Yu-Lun Hsieh ◽  
Guey-Yueh Shi ◽  
Meei-Jyh Jiang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Platelet Adhesion ◽  
Treatment Time ◽  
Shape Change ◽  
Umbilical Vein ◽  
Tissue Type ◽  
Apical Surface ◽  
Plasminogen Activation

SummaryTo investigate whether the endothelium-platelet interactions may be altered by plasminogen activation, cultured human umbilical vein endothelial cells (ECs) were treated with tissue-type plasminogen activator (t-PA) in the presence of plasminogen, and platelet adhesion to ECs was subsequently measured by using a tapered flow chamber. Our results demonstrated that platelets adhered more readily to t-PA treated EC monolayer than to the control monolayer at all shear stress levels tested. This phenomenon was treatment time-dependent and dose-dependent, and it could be blocked by adding plasmin inhibitors, such as e-amino caproic acid and aprotinin. Adherent platelets on t-PA treated EC monolayer underwent more severe shape change than those on the control monolayer. While the extracellular matrix directly treated with t-PA attracted less platelets than the control matrix did, platelet adhesion to the matrix that was produced by t-PA-treated ECs was unaltered. These data suggest that t-PA treatment on ECs compromised antiplatelet-adhesion capability on their apical surface without altering the reactivity of their extracellular matrix towards platelets.

Desmopressin (DDAVP) Enhances Platelet Adhesion to the Extracellular Matrix of Cultured Human Endothelial Cells through Increased Expression of Tissue Factor

1997 ◽  
Vol 77 (05) ◽  
pp. 0975-0980 ◽  
Author(s):  
Angel Gálvez ◽  
Goretti Gómez-Ortiz ◽  
Maribel Díaz-Ricart ◽  
Ginés Escolar ◽  
Rogelio González-Sarmiento ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Tissue Factor ◽  
Platelet Adhesion ◽  
Umbilical Vein ◽  
Procoagulant Activity ◽  
Experimental Conditions ◽  
Chromogenic Assay

SummaryThe effect of desmopressin (DDAVP) on thrombogenicity, expression of tissue factor and procoagulant activity (PCA) of extracellular matrix (ECM) generated by human umbilical vein endothelial cells cultures (HUVEC), was studied under different experimental conditions. HUVEC were incubated with DDAVP (1, 5 and 30 ng/ml) and then detached from their ECM. The reactivity towards platelets of this ECM was tested in a perfusion system. Coverslips covered with DD A VP-treated ECMs were inserted in a parallel-plate chamber and exposed to normal blood anticoagulated with low molecular weight heparin (Fragmin®, 20 U/ml). Perfusions were run for 5 min at a shear rate of 800 s1. Deposition of platelets on ECMs was significantly increased with respect to control ECMs when DDAVP was used at 5 and 30 ng/ml (p <0.05 and p <0.01 respectively). The increase in platelet deposition was prevented by incubation of ECMs with an antibody against human tissue factor prior to perfusion. Immunofluorescence studies positively detected tissue factor antigen on DDAVP derived ECMs. A chromogenic assay performed under standardized conditions revealed a statistically significant increase in the procoagulant activity of the ECMs produced by ECs incubated with 30 ng/ml DDAVP (p <0.01 vs. control samples). Northern blot analysis revealed increased levels of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate that DDAVP in vitro enhances platelet adhesion to the ECMs through increased expression of tissue factor. A similar increase in the expression of tissue factor might contribute to the in vivo hemostatic effect of DDAVP.

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