scholarly journals Effects of plasma from hibernating ground squirrels on monocyte-endothelial cell adhesive interactions

1997 ◽  
Vol 273 (6) ◽  
pp. R1861-R1869 ◽  
Author(s):  
Yoshihide Yasuma ◽  
Richard M. McCarron ◽  
Maria Spatz ◽  
John M. Hallenbeck
Keyword(s):  
Leukocyte Adhesion ◽  
Ground Squirrels ◽  
Intercellular Adhesion Molecule ◽  
Monocyte Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Mechanism ◽  
Ischemic Tissue ◽  
Adhesive Interactions ◽  
Natural Tolerance

Adhesion and subsequent penetration of leukocytes into central nervous system ischemic tissue proceeds via a coordinated inflammatory mechanism involving adhesion molecules at the blood-endothelium interface. Mammalian hibernation is a state of natural tolerance to severely reduced blood flow-oxygen delivery (i.e., ischemia). Hibernating thirteen-lined ground squirrels were investigated in an attempt to identify factors responsible for regulating this tolerance. Since leukocytopenia is closely associated with entrance into hibernation, the role of leukocyte adhesion to endothelium in this phenomenon was examined. Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelium and regulates interactions with circulating leukocytes that may result in margination or extravasation. ICAM-1 expression by rat cerebral microvascular endothelial cells (EC) cultured with plasma from hibernating (HP) or nonhibernating (NHP) thirteen-lined ground squirrels was dose dependently increased by HP and, to a lesser extent, by NHP. Treatment of EC with HP coincidentally induced significantly greater increases in monocyte adhesion to EC (37.2%) than were observed with NHP (23.9%). Study of the effects of HP and NHP on monocyte adhesion to EC may identify mechanisms responsible for ischemic tolerance in hibernators and could lead to the development of novel therapeutic approaches to the treatment of stroke.

Role of ICAM-1 in chronic hepatic allograft rejection in the rat

2002 ◽  
Vol 283 (1) ◽  
pp. G196-G203 ◽  
Author(s):  
John Wong ◽  
Paul Kubes ◽  
Yikun Zhang ◽  
Yang Li ◽  
Stefan J. Urbanski ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Brown Norway ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Recruitment ◽  
Hepatic Allograft

The pathogenesis of hepatic allograft rejection remains unclear. We aimed to clarify the early role of intercellular adhesion molecule-1 (ICAM-1)-mediated cell recruitment in chronic hepatic rejection. Liver transplantation was performed from Lewis to Lewis rats (isograft controls) and from Lewis to Brown Norway rats (allograft rejection group). The allografted rats were treated with either ICAM-1 antisense oligonucleotides (10 mg · kg−1· day−1× 6 days ip) or a control preparation (either ICAM-1 missense oligonucleotide or normal saline). Hepatic leukocyte recruitment in vivo was studied on day 6 by using intravital microscopy. Liver histology, biochemistry, and survival rates were also examined. Leukocyte adhesion in terminal hepatic venules was significantly increased in the rejection group compared with isograft controls. Antisense ICAM-1 in the allografted group effectively reduced leukocyte adhesion. Histology and liver chemistry were less deranged in the antisense-treated groups compared with control-treated allografted rats. In the allograft groups, survival was significantly prolonged in the antisense-treated rats (42.3 ± 1.2 days) compared with the controls (25.2 ± 2.7 days). These results showed that early leukocyte recruitment in the hepatic microvasculature of rejecting allografts is ICAM-1 dependent and suggest that impacting on early cell recruitment can significantly ameliorate chronic rejection.

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)

Abstract 171: Role of α-Actinin-4-Dependent Endothelial Cell Stiffness in Neutrophil Transmigration

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Peter Hordijk ◽  
Antje Schaefer ◽  
Joost te Riet ◽  
Katje Ritz ◽  
Mark Hoogenboezem ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Feedback Loop ◽  
Leukocyte Adhesion ◽  
Cell Stiffness ◽  
Intercellular Adhesion Molecule ◽  
Ageing Population ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Lining ◽  
Human Disorders

Inflammation is causally linked to many chronic human disorders and constitutes a growing problem in the ageing population. The inflammatory process is driven by interactions of activated leukocytes with the endothelial lining of blood vessels. This requires binding of leukocyte β2-integrins to endothelial ICAM-1 (InterCellular Adhesion Molecule-1), which allows leukocyte adhesion, spreading, crawling and transendothelial migration (TEM). Integrin binding induces ICAM-1 clustering and its consequent association to F-actin which enforces leukocyte adhesion. Here, we analyzed the molecular basis of this positive feedback loop. We show that ICAM-1 clustering promotes its binding to F-actin through distinct complexes with FilaminB, Cortactin and α-Actinin-4. We found that α-Actinin-4 regulates endothelial cell peripheral stiffness, which is sensed by adherent neutrophils and promotes adhesion, spreading, crawling and TEM. Conversely, increasing endothelial cell stiffness stimulates the ICAM-1-α-Actinin-4 interaction. Finally, we found that the endothelial lining of atherosclerotic plaques, which is characterized by increased stiffness and leukocyte infiltration, shows increased expression of α-Actinin-4. These results identify α-Actinin-4-regulated endothelial cell stiffness as a novel pro-inflammatory event that promotes ICAM-1-mediated leukocyte adhesion and TEM.

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.

Selectin-independent leukocyte rolling and adhesion in mice deficient in E-, P-, and L-selectin and ICAM-1

2001 ◽  
Vol 280 (2) ◽  
pp. H634-H641 ◽  
Author(s):  
S. Bradley Forlow ◽  
Klaus Ley
Keyword(s):  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Striking Similarity ◽  
Leukocyte Rolling ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Recruitment ◽  
Adhesion Efficiency

To study selectin-independent leukocyte recruitment and the role of intercellular adhesion molecule-1 (ICAM-1), we generated mice lacking all three selectins and ICAM-1 (E/P/L/I−/−) by bone marrow transplantation. These mice were viable and appeared healthy under vivarium conditions, although they showed a 97% reduction in leukocyte rolling, a 63% reduction in leukocyte firm adhesion, and a 99% reduction of neutrophil recruitment in a thioglycollate-induced model of peritonitis at 4 and 24 h. Mononuclear cell recruitment was almost unaffected. All residual leukocyte rolling and most leukocyte adhesion in these mice depended on α4-integrins, but a small number of leukocytes (6% of wild-type control) still became adherent in the absence of all known rolling mechanisms (E-, P-, L-selectin and α4-integrins). A striking similarity of leukocyte adhesion efficiency in E/P/L−/− and E/P/I−/− mice suggests a pathway in which leukocyte rolling through L-selectin requires ICAM-1 for adhesion and recruitment. Comparison of our data with mice lacking individual or other combinations of adhesion molecules reveal that elimination of more adhesion molecules further reduces leukocyte recruitment but the effect is less than additive.

scholarly journals Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats

1994 ◽  
Vol 267 (6) ◽  
pp. H2491-H2497 ◽  
Author(s):  
R. M. McCarron ◽  
L. Wang ◽  
A. L. Siren ◽  
M. Spatz ◽  
J. M. Hallenbeck
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Monocyte Adhesion ◽  
Blood Monocytes ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Stroke Risk Factor ◽  
Adhesive Interactions

The stroke risk factor hypertension may function as a predisposing agent by increasing the vulnerability of blood vessels to thrombosis or hemorrhage. The research here demonstrates that cerebrovascular endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) rats exhibit similar levels of adhesiveness for syngeneic peripheral blood monocytes (e.g., 22.53 +/- 1.32 and 24.35 +/- 1.16%, respectively). Monocyte adhesion to SHR EC was dramatically increased by treatment of EC with lipopolysaccharide, interferon-gamma, or interleukin-1 beta and tumor necrosis factor-alpha (e.g., 106, 68, and 171%, respectively). Identical treatment of WKY EC also increased adhesion albeit at significantly lower levels than observed on concomitantly tested SHR EC (e.g., 47.8, 12.7, and 60.7%, respectively). Allogeneic combinations of monocytes and EC again demonstrated significantly more upregulation of adhesion by treatment of SHR EC than WKY EC. Characterization of these adhesive interactions revealed the interplay of adhesion pathways, which include lymphocyte functional antigen-1/intercellular adhesion molecule-1 (ICAM-1), Mac-1/ICAM-1, and very late activation antigen-4/vascular adhesion molecule-1 as well as other undetermined mechanisms. In summary, these findings indicate hypertension may enhance responsiveness of endothelium to factors that promote monocyte adhesion.

LPS pretreatment ameliorates peritonitis-induced myocardial inflammation and dysfunction: role of myocytes

1999 ◽  
Vol 277 (3) ◽  
pp. H885-H892 ◽  
Author(s):  
Remi R. Neviere ◽  
Gediminas Cepinskas ◽  
W. Sean Madorin ◽  
Nina Hoque ◽  
Morris Karmazyn ◽  
...  
Keyword(s):  
Contractile Function ◽  
Leukocyte Adhesion ◽  
Cecal Ligation ◽  
Left Ventricular ◽  
Intercellular Adhesion Molecule ◽  
Myocardial Inflammation ◽  
Intercellular Adhesion Molecule 1 ◽  
Developed Pressure ◽  
Parenchymal Cells

Peritonitis induced by cecal ligation and puncture (CLP) produces a systemic inflammatory response that can be largely mitigated by pretreatment of the animals with lipopolysaccharide (LPS tolerance). Although cells of myeloid origin and endothelial cells have been shown to contribute to the development of LPS tolerance, little is known regarding the potential role of parenchymal cells in this phenomenon. The major aim of the present study was to assess whether cardiac parenchymal cells (myocytes) contribute to the development of LPS tolerance. Six hours after induction of CLP rats were neutropenic and acidotic, the myocardium contained a leukocyte infiltrate [myeloperoxidase (MPO) activity was increased], and myocardial contractile function was impaired (left ventricular developed pressure was decreased). In animals that were pretreated with LPS these manifestations of sepsis were largely reversed. Further studies focused on the responses of cardiac myocytes to CLP and whether myocytes contributed to the development of LPS tolerance. Myocytes were isolated from rat hearts 6 h after induction of CLP. These myocytes 1) exhibited an impaired ability to shorten in response to pacing, 2) contained the nuclear transcription factor NF-κB in their nuclei, 3) increased their surface levels of intercellular adhesion molecule-1 (ICAM-1), and 4) were hyperadhesive for neutrophils. All of these events did not occur in myocytes obtained from animals that were pretreated with LPS before induction of CLP. These findings indicate that LPS tolerance can be induced in myocytes with respect to polymorphonuclear leukocyte adhesion, presumably by an inability of CLP to mobilize NF-κB to the myocyte nuclei and, thereby, preventing an increase in surface levels of ICAM-1.

scholarly journals Bradykinin-induced proinflammatory signaling mechanisms

2002 ◽  
Vol 283 (6) ◽  
pp. H2676-H2686 ◽  
Author(s):  
Sakuji Shigematsu ◽  
Shuji Ishida ◽  
Dean C. Gute ◽  
Ronald J. Korthuis
Keyword(s):  
Leukocyte Adhesion ◽  
Platelet Activating Factor ◽  
Intercellular Adhesion Molecule ◽  
Concomitant Treatment ◽  
Intercellular Adhesion Molecule 1 ◽  
Rat Mesentery ◽  
A Cell ◽  
Adhesive Interactions ◽  
Oxide Synthase ◽  
Cytochrome P 450

Intravital microscopic techniques were used to examine the mechanisms underlying bradykinin-induced leukocyte/endothelial cell adhesive interactions (LECA) and venular protein leakage (VPL) in single postcapillary venules of the rat mesentery. The effects of bradykinin superfusion to increase LECA and VPL were prevented by coincident topical application of either a bradykinin-B2 receptor antagonist, a cell-permeant superoxide dismutase (SOD) mimetic or antioxidant, or inhibitors of cytochrome P-450 epoxygenase (CYPE) or protein kinase C (PKC) but not by concomitant treatment with either SOD, a mast cell stabilizer, or inhibitors of nitric oxide synthase, cyclooxygenase, xanthine oxidase, NADPH oxidase, or platelet-activating factor. Immunoneutralizing P-selectin or intercellular adhesion molecule-1 (ICAM-1) completely prevented bradykinin-induced leukocyte adhesion and emigration but did not affect VPL. On the other hand, stabilization of F-actin with phalloidin prevented bradykinin-induced leukocyte emigration and VPL but did not alter leukocyte adhesion. These data indicate that bradykinin induces LECA in rat mesenteric venules via a B2-receptor-initiated, CYPE-, oxidant- and PKC-mediated, P-selectin- and ICAM-1-dependent mechanism. Bradykinin also produced VPL, an effect that was initiated by stimulation of B2receptors and involved CYPE and PKC activation, oxidant generation, and cytoskeletal reorganization but was independent of leukocyte adherence and emigration.

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