NO donors prevent integrin-induced leukocyte adhesion but not P-selectin-dependent rolling in postischemic venules

1994 ◽  
Vol 267 (3) ◽  
pp. H931-H937 ◽  
Author(s):  
P. Kubes ◽  
I. Kurose ◽  
D. N. Granger
Keyword(s):  
Shear Rate ◽  
Tissue Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
No Donor ◽  
No Donors ◽  
In Vitro Data

The objective of this study was to examine the effect of nitric oxide (NO) donors on polymorphonuclear leukocyte (PMN) interactions in the microvasculature of postischemic tissue and to compare the antiadhesive properties of NO donors with the responses observed after immunoneutralization of three key adhesion glycoproteins (CD11/CD18, intercellular adhesion molecule-1, and P-selectin). Rolling and firm adhesion (adherence) of leukocytes and shear rate were monitored in cat mesenteric venules subjected to 60 min of ischemia (blood flow reduced to 20% of control), followed by 60 min of reperfusion. Immediately before reperfusion, the mesentery was superfused with a NO donor (3-morpholinosydonimine-N-ethyl-carbamide or spermine-NO) or a monoclonal antibody (MAb) against an adhesion glycoprotein that was administered intravenously. In untreated animals, a profound influx in rolling PMNs was observed during reperfusion that was subsequently followed by increased firm adhesion. The anti-P-selectin antibody completely abolished the rise in the flux of rolling PMNs, whereas the anti-CD18 antibody prevented firm adhesion. Both NO donors attenuated ischemia/reperfusion-induced leukocyte adhesion to a level comparable with that observed after administration of a MAb against CD11/CD18 without affecting PMN rolling. The antiadhesive effect of the NO donors could not be attributed solely to an improvement of venular wall shear rate. In vitro data did not reveal a direct effect of NO donors on the expression of CD18 or neutrophil adhesion to endothelial cells. These observations suggest that NO donors may provide protection from tissue injury by preventing PMN adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals PR-39, a proline/arginine-rich antimicrobial peptide, prevents postischemic microvascular dysfunction

1999 ◽  
Vol 277 (3) ◽  
pp. H1007-H1013 ◽  
Author(s):  
Ronald J. Korthuis ◽  
Dean C. Gute ◽  
Frank Blecha ◽  
Chris R. Ross
Keyword(s):  
Time Course ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Protein Leakage ◽  
Oxidant Production

We and others have previously demonstrated that intestinal ischemia-reperfusion (I/R) is associated with a large increase in oxidant production that contributes to microvascular barrier disruption in the small bowel. It has been suggested that the bulk of tissue damage during reperfusion can be attributed to adherent, activated neutrophils. From these observations, we hypothesized that pretreatment with PR-39, an endogenous neutrophil antibacterial peptide that is also a potent inhibitor of the neutrophil NADPH oxidase, would prevent postischemic oxidant production and the development of oxidant-dependent sequelae to I/R such as increased venular protein leakage. To test this postulate, oxidant production, venular protein leakage, leukocyte adhesion, and leukocyte emigration were monitored during reperfusion in control (no ischemia) rat mesenteric venules and in mesenteric venules subjected to I/R alone or PR-39 + I/R. Treatment with a single intravenous bolus injection of PR-39 (administered at a dose to achieve an initial blood concentration of 5 μM) abolished I/R-induced leukocyte adhesion and emigration in vivo. In vitro studies indicated that PR-39 prevents platelet-activating factor-induced neutrophil chemotaxis as well as phorbol myristate acetate (PMA)-stimulated intercellular adhesion molecule-1 expression by cultured endothelial cells. PR-39 pretreatment of rat neutrophils also blocked PMA-stimulated neutrophil adhesion to activated endothelial monolayers. In vivo, I/R was associated with a marked and progressive increase in oxidant production and venular protein leakage during reperfusion, effects that were abolished by PR-39 treatment. The results of this study indicate that PR-39 completely abolishes postischemic leukocyte adhesion and emigration. The time course for inhibition of oxidant production by PR-39 suggests that its antiadhesive properties account for this effect of the peptide. PR-39 may thus be therapeutically useful for prevention of neutrophil adhesion and activation during the postischemic inflammatory response.

L-selectin and ICAM-1 mediate reperfusion injury and neutrophil adhesion in the warm ischemic mouse liver

1998 ◽  
Vol 275 (6) ◽  
pp. G1341-G1352 ◽  
Author(s):  
Surinder S. Yadav ◽  
David N. Howell ◽  
Wenshi Gao ◽  
Douglas A. Steeber ◽  
Robert C. Harland ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Mutant Mice ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. However, the mechanisms of leukocyte adhesion and the role of adhesion receptors in hepatic vasculature remain elusive. L-selectin may critically contribute to injury, priming adhesion for later action of intercellular adhesion molecule-1 (ICAM-1). Paired experiments were performed using mutant mice (L-selectin −/−, ICAM-1 −/−, and L-selectin/ICAM-1 −/−) and wild-type mice (C57BL/6) to investigate leukocyte adhesion in the ischemic liver. Leukocyte adhesion and infiltration were assessed histologically. Aspartate aminotransferase levels were significantly reduced (2- to 3-fold) in mutant vs. wild-type mice in most groups but most significantly after 90 min of partial hepatic ischemia. Leukocyte adhesion was significantly reduced in all mutant mice. Areas of microcirculatory failure, visualized by intravital microscopy, were prevalent in wild-type but virtually absent in L-selectin-deficient mice. After total hepatic ischemia for 75 or 90 min, survival was better in mutant L-selectin and L-selectin/ICAM-1 mice vs. wild-type mice and ICAM-1 mutants. In conclusion, L-selectin is critical in the pathogenesis of hepatic ischemia-reperfusion injury. Poor sinusoidal perfusion due to leukocyte adhesion and clot formation is a factor of injury and appears to involve L-selectin and ICAM-1 receptors.

scholarly journals Endothelial PI 3-kinase activity regulates lymphocyte diapedesis

2007 ◽  
Vol 293 (6) ◽  
pp. H3608-H3616 ◽  
Author(s):  
Maryam Nakhaei-Nejad ◽  
Amer M. Hussain ◽  
Qiu-Xia Zhang ◽  
Allan G. Murray
Keyword(s):  
Kinase Activity ◽  
Leukocyte Adhesion ◽  
Flow Chamber ◽  
Regulatory Subunit ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Lymphocyte Migration ◽  
Actin Remodeling ◽  
Lymphocyte Adhesion

Lymphocyte recruitment to sites of inflammation involves a bidirectional series of cues between the endothelial cell (EC) and the leukocyte that culminate in lymphocyte migration into the tissue. Remodeling of the EC F-actin cytoskeleton has been observed after leukocyte adhesion, but the signals to the EC remain poorly defined. We studied the dependence of peripheral blood lymphocyte transendothelial migration (TEM) through an EC monolayer in vitro on EC phosphatidylinositol 3-kinase (PI 3-kinase) activity. Lymphocytes were perfused over cytokine-activated EC using a parallel-plate laminar flow chamber. Inhibition of EC PI 3-kinase activity using LY-294002 or wortmannin decreased lymphocyte TEM (48 ± 6 or 34 ± 7%, respectively, vs. control; mean ± SE; P < 0.05). Similarly, EC knockdown of the p85α regulatory subunit of PI 3-kinase decreased lymphocyte transmigration. Treatment of EC with jasplakinolide to inhibit EC F-actin remodeling also decreased lymphocyte TEM to 24 ± 10% vs. control ( P < 0.05). EC PI 3-kinase inhibition did not change the strength of lymphocyte adhesion to the EC or formation of the EC “docking structure” after intercellular adhesion molecule-1 ligation, whereas this was inhibited by jasplakinolide treatment. A similar fraction of lymphocytes migrated on control or LY-294002-treated EC and localized to interendothelial junctions. However, lymphocytes failed to extend processes below the level of vascular endothelial (VE)-cadherin on LY-294002-treated EC. Together these observations indicate that EC PI 3-kinase activity and F-actin remodeling are required during lymphocyte diapedesis and identify a PI 3-kinase-dependent step following initial separation of the VE-cadherin barrier.

scholarly journals An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium

2006 ◽  
Vol 203 (12) ◽  
pp. 2763-2777 ◽  
Author(s):  
Louise A. Johnson ◽  
Steven Clasper ◽  
Andrew P. Holt ◽  
Patricia F. Lalor ◽  
Dilair Baban ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Lymphatic Vessels ◽  
Contact Hypersensitivity ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Leukocyte Transmigration ◽  
Antiinflammatory Therapy ◽  
Skin Contact

The exit of antigen-presenting cells and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such an exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels are unknown. We show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LECs), leading to expression of the key leukocyte adhesion receptors intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of dendritic cells (DCs) via afferent lymphatics. Lastly, we show that tumor necrosis factor α stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking monoclonal antibodies. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for antiinflammatory therapy.

scholarly journals Absolute requirement of CD11/CD18 adhesion molecules, FcRII and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1484-1490 ◽  
Author(s):  
BH Kushner ◽  
NK Cheung
Keyword(s):  
Monoclonal Antibody ◽  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Neuroblastoma Cell ◽  
Intercellular Adhesion Molecule ◽  
Target Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Gm Csf

We have previously shown that 3F8, a murine IgG3, monoclonal antibody (MoAb) specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo. We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in 3F8-mediated cytotoxicity (ADCC) of human GD2 (+) melanoma and neuroblastoma cell lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CD11b, CD11c, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel of different MoAbs to CD11a had no significant inhibitory effect on ADCC, a finding consistent with the low-to-absent expression of the CD11a ligand, intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage colony-stimulating factor (GM- CSF) significantly increased the expression of CD11b, CD11c, and CD18 on normal PMN, decreased the expression of Fc receptors (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRII and FcRIII each efficiently blocked ADCC; anti-FcRI MoAb had no effect. Flow cytometry using anti-FcRII MoAb versus anti-FcRIII MoAb did not show cross competition, suggesting that inhibition of ADCC was not a steric effect resulting from FcRII proximity to FcRIII. PMN deficient in FcRIII (obtained from patients with paroxysmal nocturnal hemoglobinuria) and PMN depleted of FcRIII by treatment with elastase or phosphatidylinositol (PI)-specific phospholipase C produced low ADCC, supporting a role for the PI-liked FcRIII. Thus, optimal ADCC using human PMN, human solid tumor cells, and a clinically active MoAb (conditions that contrast with the heterologous antibodies and nonhuman or nonneoplastic targets used in most models of PMN ADCC) required CD11b, CD11c, FcRII, and the PI-linked FcRIII. Furthermore, in this clinically relevant system, GM-CSF enhancement of antitumor PMN ADCC correlated with increased expression of CD11/CD18 molecules.

Role of Mac-1 and ICAM-1 in ischemia-reperfusion injury in a microcirculation model of BALB/C mice

1994 ◽  
Vol 267 (4) ◽  
pp. H1320-H1328 ◽  
Author(s):  
D. Nolte ◽  
R. Hecht ◽  
P. Schmid ◽  
A. Botzlar ◽  
M. D. Menger ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Fluorescein Isothiocyanate ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Capillary Perfusion ◽  
Inflammatory Reactions

The leukocyte beta 2-integrin Mac-1 (CD11b/CD18) and its endothelial ligand intercellular adhesion molecule 1 (ICAM-1) are involved in leukocyte adhesion to and macromolecular leakage from postcapillary venules during inflammatory reactions. Both events are also encountered after ischemia-reperfusion of striated muscle, suggesting a central role of both adhesion proteins in reperfusion injury. Using intravital fluorescence microscopy and a microcirculation model in awake BALB/C mice, we investigated the effects of monoclonal antibodies (MAb) and Fab fragments to Mac-1 and MAb to ICAM-1 on leukocyte-endothelium interaction and macromolecular leakage of fluorescein isothiocyanate-dextran (1.5 x 10(5) mol wt) in striated skin muscle after 3 h of ischemia followed by reperfusion. We demonstrated that administration of MAb and Fab to Mac-1 before reperfusion was as effective as administration of MAb to ICAM-1, which was found to be significantly upregulated in the postischemic tissue by immunohistochemical analysis, in preventing postischemic leukocyte adhesion to and macromolecular leakage from postcapillary venules, whereas postischemic leukocyte rolling was not affected after MAb administration. Postischemic capillary perfusion was efficiently preserved in animals treated with anti-Mac-1 and anti-ICAM-1 MAb compared with animals receiving the isotype-matched control antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Role of Hyphal Formation in Interactions ofCandida albicans with Endothelial Cells

2000 ◽  
Vol 68 (6) ◽  
pp. 3485-3490 ◽  
Author(s):  
Quynh T. Phan ◽  
Paul H. Belanger ◽  
Scott G. Filler
Keyword(s):  
Endothelial Cells ◽  
Leukocyte Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Proinflammatory Response ◽  
Regulatory Pathways ◽  
Ofcandida Albicans ◽  
Hyphal Formation

ABSTRACT The ability to change from yeast to hyphal morphology is a major virulence determinant of Candida albicans. Mutants with defined defects in filamentation regulatory pathways have reduced virulence in mice. However, is it poorly understood why hyphal formation is critical for C. albicans to cause hematogenously disseminated infections. We used recently constructed mutants to examine the role of hyphal formation in the interactions ofC. albicans with endothelial cells in vitro. These interactions included the ability of the mutants to invade and injure endothelial cells. Because the formation of hyphae may influence the host inflammatory response to C. albicans, we also investigated the capacity of these mutants to stimulate endothelial cells to express E-selectin and intercellular adhesion molecule 1. We infected endothelial cells with C. albicans strains containing homozygous null mutations in the following filamentation regulatory genes: CLA4, CPH1,EFG1, and TUP1. Whereas the wild-type strain formed true hyphae on endothelial cells, we found that neither the Δefg1 nor the Δcph1 Δefg1double mutant germinated. The Δtup1 mutant formed only pseudohyphae. We also found that the Δefg1, Δcph1 Δefg1, and Δtup1 mutants had significantly reduced capacities to invade and injure endothelial cells. Therefore, Efg1p and Tup1p contribute to virulence by regulating hyphal formation and the factors that enable C. albicans to invade and injure endothelial cells. With the exception of the Δcph1 Δefg1 mutant, all other mutants stimulated endothelial cells to express at least one of the leukocyte adhesion molecules. Therefore, the combined activities of Cph1p and Efg1p are required for C. albicans to stimulate a proinflammatory response in endothelial cells.

scholarly journals Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 805-811 ◽  
Author(s):  
TK Kishimoto ◽  
RA Warnock ◽  
MA Jutila ◽  
EC Butcher ◽  
C Lane ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Neutrophil Function ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1

Neutrophil adhesion to interleukin-1 (IL-1)-stimulated human umbilical vein endothelial cells (HUVEC) involves the CD18 family of leukocyte integrins (lymphocyte function-associated antigen-1 [LFA-1], Mac-1, and p150,95) and LECAM-1 (DREG-56/LEU-8/LAM-1 antigen) on neutrophils and intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) on the endothelium. In this study, we compare CD18-independent adhesion pathways mediated by neutrophil LECAM- 1 and endothelial ELAM-1 and find that these two pathways overlap in a variety of assays: (1) anti-LECAM-1 and anti-ELAM-1 monoclonal antibody (MoAb) inhibit neutrophil binding to HUVEC, and the inhibitory effect is not additive; (2) anti-LECAM-1 MoAb, like anti-ELAM-1 MoAb, inhibits neutrophil binding to HUVEC stimulated for 3 hours with IL-1, but not to HUVEC stimulated for 8 hours, by which time ELAM-1 expression is downregulated; (3) anti-ELAM-1 MoAb has no effect on transendothelial migration, a CD18-dependent, LECAM-1-independent neutrophil function. Interestingly, anti-ELAM MoAb has a reduced but significant inhibitory effect on the adhesion of activated neutrophils that have shed their cell-surface LECAM-1. We also show that neutrophil binding to ELAM-1- transfected L cells is inhibited not only by anti-ELAM-1 but also by anti-LECAM-1 MoAb. These results suggest that LECAM-1 and ELAM-1 can operate in the same adhesion pathway, possibly as a receptor- counterreceptor pair. LECAM-1 and ELAM-1 are likely to interact with other ligands as well, perhaps through carbohydrate determinants that modify more than one glycoprotein.

scholarly journals Effects of Sevoflurane on Apoptosis of Myocardial Cells in IRI Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Shikun Zhang ◽  
Xiaoyan Du ◽  
Kun Zhang ◽  
Haiyan Wang
Keyword(s):  
Adhesion Molecule ◽  
Ischemia Reperfusion ◽  
B Cell Lymphoma ◽  
Intercellular Adhesion Molecule ◽  
Myocardial Cells ◽  
General Anesthetic ◽  
Intercellular Adhesion Molecule 1 ◽  
Immunocytochemical Assay ◽  
Underlying Mechanisms

Background. Cardiomyocyte apoptosis functions essentially in ischemia/reperfusion- (I/R-) induced myocardial injury. It is suggested that autophagy is widely implicated in the regulation of cell survival and death. Sevoflurane, as a largely used inhalational general anesthetic, has been shown to have a protective effect on cardiomyocytes. However, it was yet elusive on the underlying mechanisms. Aim. The objective of this study is to investigate the association of sevoflurane-mediated cardioprotective effects with autophagy regulation. Methods. An in vitro hypoxia model was established in primary cardiomyocytes from fresh myocardial tissue of the rats. The apoptosis rate of myocardial cells treated with hypoxia and treated with sevoflurane was measured. Western blot and immunocytochemical assay were used to measure the protein expression. The cell proliferation rate and cell apoptosis were measured using the MTT assay and flow cytometry, respectively. Results. The expression of apoptotic proteins including B cell lymphoma-2 (Bcl-2), CCAAT/enhancer-binding protein homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and Bcl-2-associated X protein (BAX) in myocardium treated with sevoflurane was significantly lower than that in myocardium treated with hypoxia. The expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in myocardium treated with sevoflurane was higher than that in myocardium treated with hypoxia, suggesting better connectivity of the myocardium. Conclusion. Sevoflurane treatment reduced the apoptosis of myocardial cells after hypoxia treatment.

Sign in / Sign up

Export Citation Format

Share Document