scholarly journals Studies of Bending Effects of Microvilli of Leukocyte on Rolling Adhesion

2018 ◽  
Author(s):  
Tai-Hsien Wu ◽  
Dewei Qi
Keyword(s):  
Leukocyte Adhesion ◽  
Underlying Mechanism ◽  
Immersed Boundary ◽  
Flexural Stiffness ◽  
Leukocyte Rolling ◽  
Rolling Velocity ◽  
Bending Deformation ◽  
Shear Rates ◽  
Lattice Spring Model ◽  
Boltzmann Lattice

AbstractIt has been widely acknowledged that further understanding about the cell adhesion (e.g., leukocyte rolling adhesion) can help us gain more knowledge about the causes of relevant diseases and design more effective treatments and diagnoses. Although recent simulation studies considered the deformability of the leukocytes, most of them, however, did not consider the bending deformation of microvilli. In this paper, an advanced leukocyte model based on an immersed boundary lattice-Boltzmann lattice-spring model (LLM) and an adhesive dynamics (AD) is presented in details. The flexural stiffness of microvilli is introduced into the model for simulations of leukocyte rolling adhesion. This innovative model is applied to investigate the influences of bending deformation of microvilli on the process of leukocyte rolling adhesion and the underlying mechanism at different shear rates. It is demonstrated that the bending deformation of microvilli can be influenced by the flexural stiffness of microvilli and shear rates, resulting in the different rolling velocity of leukocytes, number of receptor-ligand bonds, and bond forces. The findings clearly indicate that the bending of microvilli plays a crucial role in the dynamics of leukocyte adhesion.

Leukocyte adhesion in local versus hemorrhage-induced ischemia

1992 ◽  
Vol 263 (3) ◽  
pp. H810-H815 ◽  
Author(s):  
M. A. Perry ◽  
D. N. Granger
Keyword(s):  
Endothelial Cell ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Local Ischemia ◽  
Cell Adhesive ◽  
Local Restriction ◽  
Adhesive Interactions

The objective of this study was to compare the leukocyte-endothelial cell adhesive interactions elicited in postcapillary venules by either local ischemia-reperfusion or hemorrhage-reperfusion. Leukocyte rolling, adherence, and emigration were monitored in cat mesenteric venules exposed to an 85% reduction in blood flow (induced by either hemorrhage or local restriction of arterial inflow) for 1 h, followed by 1 h reperfusion. Leukocyte-endothelial cell interactions, venular diameter, and red blood cell velocity were measured during baseline, ischemia, and reperfusion periods. Both local and hemorrhage-induced ischemia reperfusion caused a reduction in leukocyte rolling velocity and increases in leukocyte adherence and emigration. Quantitatively, the adherence and emigration responses in both ischemia models were nearly identical. However, the two models differed in their response to immunoneutralization of the leukocyte adhesion glycoprotein CD11/CD18 with monoclonal antibody (MAb) IB4. The MAb had a more profound effect in attenuating leukocyte adherence and emigration in the local ischemia model. These results indicate that different factors may contribute to leukocyte-endothelial cell adhesive interactions observed in local vs. systemic models of ischemia-reperfusion.

scholarly journals TNF-α activation of arterioles and venules alters distribution and levels of ICAM-1 and affects leukocyte-endothelial cell interactions

2006 ◽  
Vol 291 (5) ◽  
pp. H2116-H2125 ◽  
Author(s):  
Ronen Sumagin ◽  
Ingrid H. Sarelius
Keyword(s):  
Spatial Distribution ◽  
Endothelial Cell ◽  
Inflammatory Responses ◽  
Leukocyte Adhesion ◽  
Leukocyte Rolling ◽  
Cremaster Muscle ◽  
Rolling Velocity ◽  
Tnf Α ◽  
Arteriolar Wall ◽  
Microvessel Wall

The observation that leukocyte-endothelial cell (EC) interactions are localized to specific regions on the microvessel wall suggests that adhesion molecule distribution is not uniform. We investigated ICAM-1 distribution and leukocyte-EC interactions in blood-perfused microvessels (<80 μm) in cremaster muscle of anesthetized mice, using intravital confocal microscopy and immunofluorescent labeling. Variability of ICAM-1 expression directly determines leukocyte adhesion distribution within the venular microcirculation and contributes to leukocyte rolling in arterioles during inflammation. The number of rolling interactions increased with ICAM-1 intensity ( r2 = 0.69, P < 0.05), and rolling velocity was lower in regions of higher ICAM-1 intensity. In controls, venular ICAM-1 expression was approximately twofold higher than in arterioles. After TNF-α treatment, ICAM-1 expression was significantly increased, 2.8 ± 0.2-fold in arterioles and 1.7 ± 0.2-fold in venules ( P < 0.05). ICAM-1 expression on activated arteriolar ECs only reached the level of control venular ICAM-1. Arteriolar but not venular ECs underwent redistribution of ICAM-1 among cells; some cells increased and some decreased ICAM-1 expression, magnifying the variability of ICAM-1. TNF-α treatment increased the length of bright fluorescent regions per unit vessel length (42%, control; 70%, TNF-α) along the arteriolar wall, whereas no significant change was observed in venules (60%, control; 63%, TNF-α). The spatial distribution and expression levels of adhesion molecules in the microcirculation determine the timing and placement of leukocyte interactions and hence significantly impact the inflammatory response. That arteriolar ECs respond to TNF-α by upregulation of ICAM-1, although in a different way compared with venules, suggests an explicit role for arterioles in inflammatory responses.

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 &lt; .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.

Leukocyte rolling velocity and its relation to leukocyte-endothelium adhesion and cell deformability

1996 ◽  
Vol 270 (4) ◽  
pp. H1371-H1380 ◽  
Author(s):  
H. H. Lipowsky ◽  
D. A. Scott ◽  
J. S. Cartmell
Keyword(s):  
Cytochalasin B ◽  
Theoretical Models ◽  
Leukocyte Rolling ◽  
Cell Deformability ◽  
Rolling Velocity ◽  
Shear Rates ◽  
Population Comparisons ◽  
Increased Strength ◽  
The Relationship ◽  
Strength Of Adhesion

To explore the relationship between the rolling velocity of leukocytes (VWBC) and wall shear rates (gamma), measurements of VWBC were made along the length of rat mesenteric venules in which a gradient in gamma was induced by compressing the venule with a blunted microprobe to form a stenosis in which gamma varied from 300 to 1500 s-1. For individual WBCs that rolled through stenosis, VWBC was proportional to gamma for its entire range, in contrast to previous studies that have shown a plateau in VWBC vs. gamma for the ensemble population. Comparisons of the slope of VWBC/gamma for individual cells with ensemble values of VWBC obtained in the entrance region of the stenosis were made during suffusion of the tissue with the chemoattractant N-formylmethionyl-leucyl-phenylalanine (FMLP), to increase WBC-EC adhesion and WBC stiffness, or colchicine and cytochalasin B to increase WNC deformability. Under control conditions, the slope of individual cells was significantly 20% greater than VWBC/gamma, whereas it was significantly reduced by 48% during suffusion with FMLP. With exposure to colchicine, the slope was 78% lower than VWBC/gamma and compared with control was similar in magnitude to that obtained with FMLP. Cytochalasin also reduced the slope by 22% compared with control and 34% compared with VWBC/ gamma. The diminished slopes of VWBC vs. gamma were consistent with published theoretical models that suggest a reduced slope with increased strength of adhesion of WBC deformability. It is thus concluded that the apparent plateau in VWBC vs. gamma arises due to the heterogeneity of adhesive and/or deformability properties in the ensemble population of circulating WBCs.

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.

Vascular protection by estrogen in ischemia-reperfusion injury requires endothelial nitric oxide synthase

2003 ◽  
Vol 284 (1) ◽  
pp. H133-H140 ◽  
Author(s):  
Alyson J. Prorock ◽  
Ali Hafezi-Moghadam ◽  
Victor E. Laubach ◽  
James K. Liao ◽  
Klaus Ley
Keyword(s):  
Nitric Oxide ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Strong Dependence ◽  
Fold Increase ◽  
No Production ◽  
Leukocyte Rolling ◽  
Vascular Protection ◽  
Rolling Velocity

Estrogen increases nitric oxide (NO) production by inducing the activity of endothelial NO synthase (eNOS) (Simoncini et al. Nature 407: 538, 2000). Ischemia (30 min) and reperfusion (I/R) increased the number of adherent leukocytes and decreased their rolling velocities in mouse cremaster muscle venules with a strong dependence on wall shear rate. Minimum rolling velocity at ∼5 min after the onset of reperfusion was accompanied by increased P-selectin expression. This preceded the peak in leukocyte adhesion (at 10–15 min). In untreated wild-type mice, I/R caused a decrease of leukocyte rolling velocity from 37 to 26 μm/s and a 2.0-fold increase in leukocyte adhesion. Both were completely abolished by 0.25 mg ip estrogen 1 h before surgery. In eNOS−/− mice, the decrease of leukocyte rolling velocity and increase in adhesion were similar but were only marginally improved by estrogen. We conclude that the protective effect of estrogen, as measured by leukocyte rolling and adhesion, is significantly reduced in eNOS−/− mice, suggesting that induction of eNOS activity is the major mechanism of vasoprotection by estrogen in this model.

Indomethacin-induced leukocyte adhesion in mesenteric venules: role of lipoxygenase products

1992 ◽  
Vol 262 (5) ◽  
pp. G903-G908 ◽  
Author(s):  
H. Asako ◽  
P. Kubes ◽  
J. Wallace ◽  
T. Gaginella ◽  
R. E. Wolf ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Plasma Concentrations ◽  
Mucosal Injury ◽  
Vessel Diameter ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Synthesis Inhibitor ◽  
Rolling Velocity ◽  
Beneficial Effects ◽  
Adhesive Interactions

Although the pathogenetic mechanisms underlying indomethacin-induced mucosal injury remain undefined, the results from recent studies suggest that leukocyte adherence in gastric microvessels may be an important component of this injury process. The objective of this study was to determine whether clinically relevant plasma concentrations of indomethacin promote leukocyte-endothelial cell adhesive interactions in postcapillary venules. Erythrocyte velocity, vessel diameter, leukocyte rolling velocity, and the number of adherent (stationary for greater than or equal to 30 s) and emigrated leukocytes were measured in rat mesenteric venules. Repeat measurements of all parameters were obtained within 20 min after addition of either 2.5 or 25 micrograms/ml indomethacin to the mesenteric superfusate. In some experiments, rats were pretreated with either a leukotriene (LT) synthesis inhibitor (L 663,536), an LTD4 (MK-571) or LTB4 (SC 41930) receptor antagonist, misoprostol, or prostacyclin (PGI2). Indomethacin alone increased the number of adherent leukocytes, reduced both leukocyte rolling velocity and venular shear rate, but did not promote leukocyte emigration. L 663,536 and SC 41930 prevented all of the adhesive and hemodynamic alterations induced by indomethacin; misoprostol and PGI2, but not MK-571, exerted similar beneficial effects. These results indicate that indomethacin promotes leukocyte adherence in postcapillary venules through an LTB4-dependent mechanism.

TNF-alpha induces selectin-mediated leukocyte rolling in mouse cremaster muscle arterioles

1997 ◽  
Vol 272 (3) ◽  
pp. H1391-H1400 ◽  
Author(s):  
E. J. Kunkel ◽  
U. Jung ◽  
K. Ley
Keyword(s):  
Tnf Alpha ◽  
Leukocyte Rolling ◽  
Cremaster Muscle ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Rolling Velocity ◽  
Shear Rates ◽  
Factor Alpha ◽  
Wall Shear ◽  
Deficient Mice

Leukocyte rolling is commonly restricted to venules and mediated by selectins expressed both on leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). We show here that 2- to 3-h tumor necrosis factor-alpha (TNF-alpha) stimulation of the mouse cremaster muscle induces rolling in arterioles (diameters 30-70 microm; wall shear rates 225-1,770 s(-1)). Weak P-selectin expression was detected on arteriolar endothelium of TNF-alpha-stimulated cremaster muscles. No rolling was observed in arterioles smaller than 30 microm (wall shear rates 1,500-3,250 s(-1)). The arteriolar rolling flux fraction in wild-type mice averaged approximately 5% and rolling was blocked by the P-selectin monoclonal antibody (MAb) RB40.34. Rolling in L- and E-selectin-deficient mice was similar to that in wild-type mice and was also blocked by the MAb RB40.34. Rolling was completely absent in arterioles of P-selectin-deficient mice. The average rolling velocity in arterioles of wild-type and L-selectin-deficient mice was approximately 50 microm/s but increased to approximately 110 microm/s in E-selectin-deficient mice and after injection of the blocking E-selectin MAb 9A9 in wild-type mice. We conclude that TNF-alpha treatment induces P-selectin-dependent rolling in arterioles that requires E-selectin for rolling at normal velocities.

scholarly journals Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation

2018 ◽  
Vol 50 (3) ◽  
pp. 1005-1014 ◽  
Author(s):  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Noelia Diaz-Morales ◽  
Francesca Iannantuoni ◽  
Sandra Lopez-Domenech ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Pilot Study ◽  
Leukocyte Adhesion ◽  
Flow Chamber ◽  
Leukocyte Rolling ◽  
Rolling Velocity ◽  
Vascular Walls ◽  
Biochemical Evaluation ◽  
Vitro Model

Background/Aims: There is a lack of reliable biological markers for the early diagnosis of diabetic nephropathy (DN) during type 2 diabetes. In this pilot study we aim to assess whether miR-31 levels are modulated by the presence of DN and whether the expression of this miRNA is related to leukocyte-endothelial interactions and inflammation. Methods: Thirty-one T2D patients were enrolled in this pilot study; 18 with no diabetic complications and 13 with diabetic nephropathy. 24 non-diabetic subjects and 13 T2D patients with retinopathy (absent of other complications) were included to test the specificity of miR-31. Following anthropometric and biochemical evaluation, serum miR-31 levels were assessed by Real Time-PCR. Leukocyte-endothelial interactions were evaluated by a parallel flow chamber in vitro model. Serum TNFα, IL-6 and ICAM-1 levels were determined by XMAP-technology in a flow cytometry-based Luminex 200 instrument. Results: Serum miR-31 levels were similar between control and T2D subjects. However, T2D patients with DN displayed reduced levels of miR-31 with respect to patients without complications. This decrease in miR-31 was more pronounced in patients with macroalbuminuria than in those with microalbuminuria and was specific for DN, since patients with retinopathy displayed unaltered miR-31 levels. The presence of DN involved a lower leukocyte rolling velocity and an increased rolling flux and adhesion. miR-31 levels were positively correlated with leukocyte rolling velocity and negatively associated to leukocyte adhesion, TNFα, IL-6 and ICAM-1 levels. Conclusion: Serum miR-31 may be a biomarker for DN in T2D patients. The regulation of this miRNA seems to be related to the recruitment of leukocytes to vascular walls induced by pro-inflammatory and adhesion molecules.

Leukocyte-Endothelium Interaction in the Rat Mesenteric Microcirculation during Halothane or Sevoflurane Anesthesia

1997 ◽  
Vol 87 (3) ◽  
pp. 591-598 ◽  
Author(s):  
Hiroshi Morisaki ◽  
Makoto Suematsu ◽  
Yoshiyuki Wakabayashi ◽  
Shigeaki Moro-oka ◽  
Kazuaki Fukushima ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Low Flow ◽  
Leukocyte Rolling ◽  
Sevoflurane Anesthesia ◽  
Mechanically Ventilated ◽  
Shear Rates ◽  
Flow Perfusion ◽  
Intracellular Adhesion Molecule ◽  
Wall Shear ◽  
Adhesive Interactions

Background The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules. Methods Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb 1A29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins. Results Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29. Conclusions Halothane or sevoflurane anesthesia induces venular leukocyte rolling and adhesion: P-selectin upregulation plays a crucial role in leukocyte rolling and adhesion during sevoflurane anesthesia, whereas low-flow perfusion is likely to evoke ICAM-1-dependent leukocyte adhesion during halothane anesthesia.

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