scholarly journals Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 177-185 ◽  
Author(s):  
K Ley ◽  
G Linnemann ◽  
M Meinen ◽  
LM Stoolman ◽  
P Gaehtgens
Keyword(s):  
Leukocyte Adhesion ◽  
Sulfated Polysaccharides ◽  
Leukocyte Rolling ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Adhesion Receptor ◽  
Rat Mesentery ◽  
Rolling Leukocytes ◽  
Rolling Leukocyte

Abstract Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.

scholarly journals Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 177-185 ◽  
Author(s):  
K Ley ◽  
G Linnemann ◽  
M Meinen ◽  
LM Stoolman ◽  
P Gaehtgens
Keyword(s):  
Leukocyte Adhesion ◽  
Sulfated Polysaccharides ◽  
Leukocyte Rolling ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Adhesion Receptor ◽  
Rat Mesentery ◽  
Rolling Leukocytes ◽  
Rolling Leukocyte

Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.

Heat-Sterllized Pd Fluid Blocks Leukocyte Adhesion and Increases Flow Velocity in Rat Peritoneal Venules

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 137-141 ◽  
Author(s):  
Peter Jonasson ◽  
Ulf Bagge ◽  
Anders Wieslander ◽  
Magnus Braide
Keyword(s):  
Cell Culture ◽  
Blood Flow ◽  
Flow Velocity ◽  
Bacterial Infections ◽  
Degradation Products ◽  
Leukocyte Adhesion ◽  
Microvascular Blood Flow ◽  
Leukocyte Rolling ◽  
Rat Mesentery ◽  
Rolling Leukocytes

Data from cell culture experiments indicate that heat sterilization of peritoneal dialysis (PD) fluids produces cytotoxic glucose degradation products. The present vital microscopic study investigated the effects of different sterilization methods on the biocompatibility of PD fluids. Thus, heat-sterilized (commercially obtained and experimentally produced) and filter-sterilized PD fluids (pH = 5.30 5.40; 1.5% glucose) were compared with Tyrode buffer, with respect to the effects on microvascular blood flow velocity and leukocyte adhesion in the rat mesentery. Exteriorization of the mesentery produced a mild inflammation, known from the literature and characterized by the adhesive rolling of leukocytes along venular walls. Superfusion of the mesentery with filter-sterilized PD fluid had no significant effects on leukocyte rolling or flow velocity in venules 25 40 μm in diameter compared with buffer superfusion. Heat-sterilized PD fluid decreased the concentration of rolling leukocytes and increased flow velocity significantly, as compared with buffer and filter-sterilized PD fluid. The results indicate that heat sterilization of PD fluids produces substances that interact with microvascular tone and leukocyte-endothelial adhesion, which hypothetically could impair the acute, granulocyte-mediated defense against bacterial infections.

Hydrogen peroxide induces leukocyte rolling: modulation by endogenous antioxidant mechanisms including NO

1996 ◽  
Vol 271 (2) ◽  
pp. H614-H621 ◽  
Author(s):  
B. Johnston ◽  
S. Kanwar ◽  
P. Kubes
Keyword(s):  
Nitric Oxide ◽  
Leukocyte Adhesion ◽  
Nitric Oxide Donor ◽  
Leukocyte Rolling ◽  
Endogenous Antioxidants ◽  
Endogenous Antioxidant ◽  
Rolling Leukocytes ◽  
Antioxidant Mechanisms ◽  
Antibody Inhibition

In this study, intravital microscopy was used to examine the mechanisms that regulate H2O2-induced leukocyte rolling within rat mesenteric venules in vivo. H2O2 elicited leukocyte rolling within a narrow response window between 10 and 500 microM H2O2. Continuous superfusion with 100 microM H2O2 induced a large but transient increase in the flux of rolling leukocytes, whereas a short 5-min pulse elicited a sustained increase in rolling flux. Both treatments caused increases in leukocyte adhesion. H2O2-induced increases in leukocyte flux and adhesion could be prevented with an anti-P-selectin antibody. Inhibition of endogenous catalase (aminotriazole), glutathione (diethyl maleate), or nitric oxide (NG-nitro-L-arginine methyl ester) shifted the effective concentration of H2O2; continuous superfusion with 10 microM H2O2 now elicited large and sustained increases in leukocyte rolling flux, whereas 100 microM H2O2 elicited less than optimal responses. Dual antioxidant inhibition further reduced the effective H2O2 concentration to 1 microM H2O2. A nitric oxide donor prevented the increased rolling flux induced by 100 microM H2O2. These findings suggest that endogenous antioxidants are important regulators of H2O2-induced, P-selectin-dependent leukocyte rolling in vivo.

Control of leukocyte rolling velocity in TNF-α–induced inflammation by LFA-1 and Mac-1

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 336-341 ◽  
Author(s):  
Jessica L. Dunne ◽  
Christie M. Ballantyne ◽  
Arthur L. Beaudet ◽  
Klaus Ley
Keyword(s):  
Leukocyte Adhesion ◽  
Leukocyte Rolling ◽  
Rolling Velocity ◽  
Slowing Down ◽  
Tnf Α ◽  
Adhesion Efficiency ◽  
Factor Α ◽  
Rolling Leukocytes ◽  
Necrosis Factor ◽  
Β2 Integrins

Previously it was shown that β2-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the β2-integrins, αLβ2 (LFA-1) or αMβ2 (Mac-1), were used to determine which of the β2-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factor-α and prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1−/−mice (11.0 ± 0.7 μm/s) and Mac-1−/− mice (10.1 ± 1.1 μm/s) compared to wild-type mice (4.8 ± 0.3 μm/s;P < .05), but were lower than in CD18−/−mice (28.5 ± 2.1 μm/s). When both LFA-1 and Mac-1 were absent or blocked, rolling velocity became dependent on shear rate and approached that of CD18−/− mice. In addition, leukocyte adhesion efficiency was decreased in LFA-1−/− mice to near CD18−/− levels, but decreased only slightly in Mac-1−/− mice. Thus, both LFA-1 and Mac-1 contribute to slowing down rolling leukocytes, although LFA-1 is more important than Mac-1 in efficiently inducing firm adhesion.

Molecular mechanisms involved in superoxide-induced leukocyte-endothelial cell interactions in vivo

1994 ◽  
Vol 266 (2) ◽  
pp. H637-H642 ◽  
Author(s):  
J. P. Gaboury ◽  
D. C. Anderson ◽  
P. Kubes
Keyword(s):  
Molecular Mechanisms ◽  
Leukocyte Adhesion ◽  
Platelet Activating Factor ◽  
Leukocyte Rolling ◽  
Rolling Velocity ◽  
Paf Receptor ◽  
Rolling Leukocytes ◽  
Adherent Leukocytes ◽  
Web 2086

Intravital microscopy was used to monitor leukocyte adherence, flux, rolling velocity, and number of rolling leukocytes (flux/velocity) in venules 25–40 microns in diameter. The superoxide-generating system, hypoxanthine and xanthine oxidase (HX/XO), was infused into the mesenteric circulation in untreated animals or in animals pretreated with either catalase (a hydrogen peroxide scavenger), WEB-2086 [a platelet-activating factor (PAF) receptor antagonist], or monoclonal antibodies directed against adhesion molecules CD18 (CL26) or P-selectin (PB1.3). HX/XO infusion caused a decrease in leukocyte rolling velocity and an increase in the number of rolling and adherent leukocytes. WEB-2086 prevented the increase in leukocyte adhesion and markedly increased leukocyte rolling velocity. PB1.3 abolished the HX/XO-associated rise in the flux of rolling leukocytes and proportionally decreased the number of adherent leukocytes. CL26 abolished HX/XO-induced leukocyte adhesion and also reduced the number of rolling leukocytes. In conclusion, P-selectin mediates the increased leukocyte flux induced by superoxide, whereas PAF and CD18 modulate leukocyte adhesion. PAF also reduces leukocyte rolling velocity, possibly as a result of CD18, but not P-selectin.

scholarly journals 6-C-kine (SLC), a Lymphocyte Adhesion-triggering Chemokine Expressed by High Endothelium, Is an Agonist for the MIP-3β Receptor CCR7

1998 ◽  
Vol 141 (4) ◽  
pp. 1053-1059 ◽  
Author(s):  
James J. Campbell ◽  
Edward P. Bowman ◽  
Kristine Murphy ◽  
Kenneth R. Youngman ◽  
Michael A. Siani ◽  
...  
Keyword(s):  
Lymphoid Tissue ◽  
Memory T Cells ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Common Receptor ◽  
Circulating Lymphocytes ◽  
Stromal Cell Derived Factor ◽  
Mouse Lymphocytes

The β chemokine known as 6-C-kine, secondary lymphoid-tissue chemokine (SLC), TCA4, or Exodus-2 (herein referred to as 6CK/SLC) can trigger rapid integrin-dependent arrest of lymphocytes rolling under physiological shear and is highly expressed by high endothelial venules, specialized vessels involved in lymphocyte homing from the blood into lymph nodes and Peyer's patches. We show that 6CK/SLC is an agonist for the lymphocyte chemoattractant receptor, CCR7 (EBI-1, BLR-2), previously described as a receptor for the related β chemokine MIP-3β (ELC or Exodus-3). Moreover, 6CK/SLC and MIP-3β attract the same major populations of circulating lymphocytes, including naive and memory T cells > B cells (but not natural killer cells); desensitization to MIP-3β inhibits lymphocyte chemotaxis to 6CK/SLC but not to the α chemokine SDF-1 (stromal cell–derived factor); and 6CK/SLC competes for MIP-3β binding to resting mouse lymphocytes. The findings suggest that the majority of circulating lymphocytes respond to 6CK/SLC and MIP-3β in large part through their common receptor CCR7 and that these molecules may be important mediators of physiological lymphocyte recirculation in vivo.

Sulfated polysaccharides inhibit leukocyte rolling in rabbit mesentery venules

1991 ◽  
Vol 260 (5) ◽  
pp. H1667-H1673 ◽  
Author(s):  
K. Ley ◽  
M. Cerrito ◽  
K. E. Arfors
Keyword(s):  
Heparan Sulfate ◽  
Dextran Sulfate ◽  
Dermatan Sulfate ◽  
Leukocyte Adhesion ◽  
Keratan Sulfate ◽  
Mean Value ◽  
Sulfated Polysaccharides ◽  
Leukocyte Rolling ◽  
Chondroitin Sulfates ◽  
Wide Range

Before firm adhesion, leukocytes roll slowly along the walls of small venules at velocities ranging from 0.7 to 36% of mean blood flow velocity. To investigate the nature of the adhesive process underlying leukocyte rolling, synthetic (dextran sulfate) and naturally occurring sulfated polysaccharides (heparin, chondroitin sulfates, keratan sulfate, and heparan sulfate) were infused via glass micropipettes into the lumen of small venules (20–60 microns diam) of the rabbit mesentery. Leukocyte rolling was observed and quantified using both transmitted light and incident fluorescence intravital microscopy. Rolling leukocytes accounted for 27–80% of total leukocyte flux, exhibiting a wide range of individual velocities (0.01–0.84 mm/s) with a mean value of 4% of centerline velocity. Dextran sulfate (Mr 500,000) inhibited leukocyte rolling very effectively [half-effective concentration (ED50) approximately 10 micrograms/ml] and was able to almost completely abolish rolling at 500 micrograms/ml. Heparin (ED50 approximately 50 micrograms/ml), chondroitin 6-sulfate C (ED50 approximately 500 micrograms/ml), and heparan sulfate (ED50 approximately 5 mg/ml) also reduced leukocyte rolling. At 5 mg/ml, chondroitin 4-sulfate B (dermatan sulfate) was marginally effective, but chondroitin 4-sulfate A and keratan sulfate were ineffective. The present data suggest that an adhesion receptor-ligand system distinct from the leukocyte integrins may be underlying transient leukocyte adhesion (rolling). Endothelial glycoproteins or proteoglycans containing sulfated side chains may be involved in mediating this adhesive process.

scholarly journals Threshold Levels of Fluid Shear Promote Leukocyte Adhesion through Selectins (CD62L,P,E)

1997 ◽  
Vol 136 (3) ◽  
pp. 717-727 ◽  
Author(s):  
Michael B. Lawrence ◽  
Geoffrey S. Kansas ◽  
Eric J. Kunkel ◽  
Klaus Ley
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Fluid Shear Stress ◽  
Leukocyte Adhesion ◽  
Threshold Level ◽  
Leukocyte Rolling ◽  
Fluid Shear ◽  
High Endothelial Venules ◽  
Similar Reduction ◽  
Wall Shear

Leukocyte adhesion through L-selectin to peripheral node addressin (PNAd, also known as MECA-79 antigen), an L-selectin ligand expressed on high endothelial venules, has been shown to require a minimum level of fluid shear stress to sustain rolling interactions (Finger, E.B., K.D. Puri, R. Alon, M.B. Lawrence, V.H. von Andrian, and T.A. Springer. 1996. Nature (Lond.). 379:266–269). Here, we show that fluid shear above a threshold of 0.5 dyn/cm2 wall shear stress significantly enhances HL-60 myelocyte rolling on P- and E-selectin at site densities of 200/μm2 and below. In addition, gravitational force is sufficient to detach HL60 cells from P- and E-selectin substrates in the absence, but not in the presence, of flow. It appears that fluid shear–induced torque is critical for the maintenance of leukocyte rolling. K562 cells transfected with P-selectin glycoprotein ligand-1, a ligand for P-selectin, showed a similar reduction in rolling on P-selectin as the wall shear stress was lowered below 0.5 dyn/cm2. Similarly, 300.19 cells transfected with L-selectin failed to roll on PNAd below this level of wall shear stress, indicating that the requirement for minimum levels of shear force is not cell type specific. Rolling of leukocytes mediated by the selectins could be reinitiated within seconds by increasing the level of wall shear stress, suggesting that fluid shear did not modulate receptor avidity. Intravital microscopy of cremaster muscle venules indicated that the leukocyte rolling flux fraction was reduced at blood centerline velocities less than 1 mm/s in a model in which rolling is mediated by L- and P-selectin. Similar observations were made in L-selectin–deficient mice in which leukocyte rolling is entirely P-selectin dependent. Leukocyte adhesion through all three selectins appears to be significantly enhanced by a threshold level of fluid shear stress.

scholarly journals Comprehensive analysis of lymph node stroma-expressed Ig superfamily members reveals redundant and nonredundant roles for ICAM-1, ICAM-2, and VCAM-1 in lymphocyte homing

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 915-925 ◽  
Author(s):  
Rémy T. Boscacci ◽  
Friederike Pfeiffer ◽  
Kathrin Gollmer ◽  
Ana Isabel Checa Sevilla ◽  
Ana Maria Martin ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Peripheral Lymph ◽  
The Individual ◽  
Cell Adhesion Molecule 1

Abstract Although it is well established that stromal intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and vascular cell adhesion molecule-1 (VCAM-1) mediate lymphocyte recruitment into peripheral lymph nodes (PLNs), their precise contributions to the individual steps of the lymphocyte homing cascade are not known. Here, we provide in vivo evidence for a selective function for ICAM-1 > ICAM-2 > VCAM-1 in lymphocyte arrest within noninflamed PLN microvessels. Blocking all 3 CAMs completely inhibited lymphocyte adhesion within PLN high endothelial venules (HEVs). Postarrest extravasation of T cells was a 3-step process, with optional ICAM-1–dependent intraluminal crawling followed by rapid ICAM-1– or ICAM-2–independent diapedesis and perivascular trapping. Parenchymal motility of lymphocytes was modestly reduced in the absence of ICAM-1, while ICAM-2 and α4-integrin ligands were not required for B-cell motility within follicles. Our findings highlight nonredundant functions for stromal Ig family CAMs in shear-resistant lymphocyte adhesion in steady-state HEVs, a unique role for ICAM-1 in intraluminal lymphocyte crawling but redundant roles for ICAM-1 and ICAM-2 in lymphocyte diapedesis and interstitial motility.

scholarly journals Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of L-selectin.

1993 ◽  
Vol 177 (3) ◽  
pp. 833-838 ◽  
Author(s):  
G S Kansas ◽  
K Ley ◽  
J M Munro ◽  
T F Tedder
Keyword(s):  
Amino Acid ◽  
Leukocyte Adhesion ◽  
Frozen Section ◽  
Cytoplasmic Domain ◽  
Leukocyte Rolling ◽  
High Endothelial Venules ◽  
Peripheral Lymph ◽  
Selectin Family

L-selectin (leukocyte adhesion molecule 1/MEL-14), a member of the selectin family of cell adhesion molecules, mediates leukocyte rolling and leukocyte adhesion to endothelium at sites of inflammation. In addition, L-selectin mediates the binding of lymphocytes to high endothelial venules (HEV) of peripheral lymph nodes. The strong amino acid sequence conservation of the cytoplasmic domain of L-selectin between humans and mice suggests an important role for this region. Deletion of the COOH-terminal 11 amino acids from the approximately 17 amino acid cytoplasmic domain of L-selectin eliminated binding of lymphocytes to HEV in the in vitro frozen section assay, and also abolished leukocyte rolling in vivo in exteriorized rat mesenteric venules, but did not alter the lectin activity of L-selectin. Pretreatment of cells with cytochalasin B, which disrupts actin microfilaments, also abolished adhesion without affecting carbohydrate recognition. Therefore, the cytoplasmic domain of L-selectin regulates leukocyte adhesion to endothelium independent of ligand recognition, by controlling cytoskeletal interactions and/or receptor avidity.

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