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284
Tracking Leukocytes In Vivo With Shape And Size Constrained Active Contours
, 2002
"... Inflammatory disease is initiated by leukocytes (white blood cells) rolling along the inner surface Hning of small blood vessels called postcapillary venules. Studying the number and velocity of rolling leukocytes is essential to understanding and successfully treating inflammatory diseases. Potent ..."
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Cited by 66 (20 self)
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Inflammatory disease is initiated by leukocytes (white blood cells) rolling along the inner surface Hning of small blood vessels called postcapillary venules. Studying the number and velocity of rolling leukocytes is essential to understanding and successfully treating inflammatory diseases. Potential inhibitors of leukocyte recruitment can be screened by leukocyte rolling assays and successful inhibitors validated by intravital microscopy. In this paper we present an active contour or snake-based technique to automatically track the movement of the leukocytes. The novelty of the proposed method Hes in the energy functional that constrains the shape and size of the active contour. This paper introduces a significant enhancement over existing gradientbased snakes in the form of a modified gradient vector flow. Using the gradient vector flow, we can track leukocytes rolling at high speeds that are not amenable to tracking with the existing edge-based techniques. We also propose a new energy based implicit sampling method of the points on the active contour that replaces the computationally expensive explicit method. To enhance the performance of this shape and size constrained snake model we have coupled it with Kalman f'fiter, so that during coasting (when the leukocytes are completely occluded or obscured), the tracker may infer the location of the center of the leukocyte. Finally we have compared the performance of the proposed snake tracker with that of the correlation and centroid-based trackers. The proposed snake tracker results in superior performance measures such as reduced error in locating the leukocyte under tracking and improvements in the percentage of frames successfully tracked. For screening and drug validation, the tracker shows promise as an automat...
The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling
- J
, 1997
"... Abstract. Two mechanisms have been proposed for regulating rolling velocities on selectins. These are (a) the intrinsic kinetics of bond dissociation, and (b) the reactive compliance, i.e., the susceptibility of the bond dissociation reaction to applied force. To determine which of these mechanisms ..."
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Cited by 52 (4 self)
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Abstract. Two mechanisms have been proposed for regulating rolling velocities on selectins. These are (a) the intrinsic kinetics of bond dissociation, and (b) the reactive compliance, i.e., the susceptibility of the bond dissociation reaction to applied force. To determine which of these mechanisms explains the 7.5–11.5-fold faster rolling of leukocytes on L-selectin than on E- and P-selectins, we have compared the three selectins by examining the dissociation of transient tethers. We find that the intrinsic kinetics for tether bond dissociation are 7–10-fold more rapid for L-selectin than for E- and P-selectins, and are proportional to the rolling velocities through these selectins. The durations of pauses during rolling correspond to the duration of transient tethers on low density substrates. Moreover, applied
Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res
, 1998
"... Abstract—The nuclear enzyme poly (ADP-ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of ischemia/reperfusion injury and circulatory shock. The aim of this study was to investigate whether PARS activity may modulate endothelial-neutrophil interaction. We presen ..."
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Cited by 41 (4 self)
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Abstract—The nuclear enzyme poly (ADP-ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of ischemia/reperfusion injury and circulatory shock. The aim of this study was to investigate whether PARS activity may modulate endothelial-neutrophil interaction. We present evidence that genetic disruption of PARS provides protection against myocardial ischemia and reperfusion injury by inhibiting the expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) and, consequently, by inhibiting the recruitment of neutrophils into the jeopardized tissue. Furthermore, using in vitro studies, we demonstrate that in fibroblasts lacking a functional gene for PARS, cytokine-stimulated expression of ICAM-1 is significantly reduced compared with fibroblasts from animals with a normal genotype. Similarly, in cultured human endothelial cells, oxidative- or cytokine-dependent expression of P-selectin and ICAM-1 is reduced by pharmacological inhibition of PARS by 3-aminobenzamide. These findings provide the first direct evidence that PARS activation participates in neutrophil-mediated myocardial damage by regulating the expression of P-selectin and ICAM-1 in ischemic and reperfused myocardium, and they also provide the basis for a novel therapeutic approach for the treatment of reperfusion injury. (Circ Res. 1998;83:85-94.) Key Words: nitric oxide n peroxynitrite n cell adhesion molecule n neutrophil n 3-aminobenzamide Endothelial dysfunction is an important early-recurringphenomenon in virtually all forms of ischemia and reperfusion injury. The dysfunction appears to be triggered by
The phagocytes: neutrophils and monocytes
- Blood 2008
"... The production and deployment of phago-cytes are central functions of the hemato-poietic system. In the 1950s, radioiso-topic studies demonstrated the high prodution rate and short lifespan of neu-trophils and allowed researchers to fol-low the monocytes as they moved from the marrow through the blo ..."
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Cited by 40 (0 self)
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The production and deployment of phago-cytes are central functions of the hemato-poietic system. In the 1950s, radioiso-topic studies demonstrated the high prodution rate and short lifespan of neu-trophils and allowed researchers to fol-low the monocytes as they moved from the marrow through the blood to become tissue macrophages, histiocytes, and den-dritic cells. Subsequently, the discovery of the colony-stimulating factors greatly improved understanding the regulation of phagocyte production. The discovery of the microbicidal myeloperoxidase-H2O2-halide system and the importance of NADPH oxidase to the generation of H2O2 also stimulated intense interest in phagocyte disorders. More recent re-search has focused on membrane recep-tors and the dynamics of the responses of phagocytes to external factors includ-ing immunoglobulins, complement pro-teins, cytokines, chemokines, integrins, and selectins. Phagocytes express toll-like receptors that aid in the clearance of a wide range of microbial pathogens and their products. Phagocytes are also important sources of pro- and anti-inflammatory cytokines, thus participat-ing in host defenses through a variety of mechanisms. Over the last 50 years, many genetic and molecular disorders of phago-cytes have been identified, leading to improved diagnosis and treatment of con-ditions which predispose patients to the risk of recurrent fevers and infectious diseases. (Blood. 2008;112:935-945)
Neutrophils roll on adherent neutrophils bound to cytokineinduced endothelial cells via L-selectin on the rolling cells
, 1994
"... Specific arrest of neutrophils in venules is central to their rapid accumulation during local inflammatory responses. Initial neutrophil rolling on endothelium is mediated by leukocyte L-selectin and the inducible vascular adhesion proteins P- and E-selectin. This rolling is a prerequisite for endot ..."
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Cited by 39 (1 self)
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Specific arrest of neutrophils in venules is central to their rapid accumulation during local inflammatory responses. Initial neutrophil rolling on endothelium is mediated by leukocyte L-selectin and the inducible vascular adhesion proteins P- and E-selectin. This rolling is a prerequisite for endothelial-dependent neutrophil arrest. Here we describe rolling of neutrophils on the surface of previously arrested neutrophils and demonstrate that this interaction involves L-selectin exclusively on rolling cells. The adherent neutrophil support of L-selectin-dependent neutrophil rolling in vivo can promote continuous and augmented leukocyte recruitment at sites of previous neutrophil accumulation. T he recruitment of leukocytes to sites of acute inflammation is controlled by sequential interactions that eventually lead to migration of the cell from the blood into the affected tissue. Blood-borne neutrophils recognize the endothelium of the vascular bed within the inflamed tissue, stop on the lumenal vessel wall while within the blood flow, migrate
An automatic braking system that stabilizes leukocyte rolling by an increase in selectin bond number with shear
- J. Cell
, 1999
"... Abstract. Wall shear stress in postcapillary venules varies widely within and between tissues and in response to inflammation and exercise. However, the speed at which leukocytes roll in vivo has been shown to be almost constant within a wide range of wall shear stress, i.e., force on the cell. Simi ..."
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Cited by 34 (1 self)
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Abstract. Wall shear stress in postcapillary venules varies widely within and between tissues and in response to inflammation and exercise. However, the speed at which leukocytes roll in vivo has been shown to be almost constant within a wide range of wall shear stress, i.e., force on the cell. Similarly, rolling velocities on purified selectins and their ligands in vitro tend to plateau. This may be important to enable rolling leukocytes to be exposed uniformly to activating stimuli on endothelium, independent of local hemodynamic conditions. Wall shear stress increases the rate of dissociation of individual selectin–ligand tether bonds exponentially (1, 4) thereby destabilizing rolling. We find that this is compensated by a shear-dependent increase in the number of bonds per rolling step. We also find an
Leukocyte adhesion to vascular endothelium induces E-selectin linkage to the actin cytoskeleton
- J. Cell Biol
, 1996
"... Abstract. We have examined functions of the cytoplasmic domain of E-selectin, an inducible endothelial transmembrane protein, especially its ability to associate with the cytoskeleton during leukocyte adhesion. Confocal microscopy of interleukin-1 13 (IL-113)activated human umbilical vein endothelia ..."
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Cited by 29 (7 self)
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Abstract. We have examined functions of the cytoplasmic domain of E-selectin, an inducible endothelial transmembrane protein, especially its ability to associate with the cytoskeleton during leukocyte adhesion. Confocal microscopy of interleukin-1 13 (IL-113)activated human umbilical vein endothelial cells (HUVEC) visualized clustering of E-selectin molecules in the vicinity of leukocyte-endothelial cell attachment sites. A detergent based extraction and Western blotting procedure demonstrated an association of E-selectin with the insoluble (cytoskeletal) fraction of endothelial monolayers that correlated with adhesion of leukocytes via an E-selectin-dependent mechanism. A mutant form of E-selectin lacking the cytoplasmic domain (tailless E-selectin) was expressed in COS-7 cells
E-selectin supports neutrophil rolling in vitro under conditions of
, 1993
"... E-selectin was evaluated for its ability to support neutrophil adhesion under conditions of flow. At a wall shear stress of 1.85 dyn/cm2, neutrophils were found to attach to E-selectin ex-pressed on the apical surface of L cell monolayers. The initial intercellular contact was most often evidenced b ..."
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Cited by 27 (4 self)
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E-selectin was evaluated for its ability to support neutrophil adhesion under conditions of flow. At a wall shear stress of 1.85 dyn/cm2, neutrophils were found to attach to E-selectin ex-pressed on the apical surface of L cell monolayers. The initial intercellular contact was most often evidenced by neutrophils rolling on the monolayer at a mean rate of- 10,um/s. Anti-E-selectin monoclonal antibody, CL2 /6, inhibited this interaction by> 90%. Rolling neutrophils often transiently stopped, but in contrast to the behavior on stimulated endothelial cells, they remained spherical in shape and did not migrate on or beneath the monolayer. A possible contribution of neutrophil L-selectin to this interaction was indicated by the findings that anti-L-se-lectin monoclonal antibody, DREG-56, inhibited E-selectin-dependent adhesion under flow by> 65%, and there was a highly significant correlation between surface levels of L-selec-tin and E-selectin-dependent adhesion under flow. E-selectin also appeared to support neutrophil adhesion to IL-lfl-stimu-lated endothelial cells under conditions of flow, but it accounted for only n 30 % of the level of adherence, in contrast to L-selec-tin which accounted for> 65%. Thus, both L-selectin and E-se-lectin can support neutrophil adhesion at wall shear stresses that preclude intercellular adhesion molecule-I-dependent ad-hesion, and they participate in neutrophil adherence to stimu-lated endothelial cells under conditions of flow. (J. Clin. Invest.
CD44 and its ligand hyaluronate mediate rolling under physiologic flow: a novel lymphocyte–endothelial cell primary adhesion pathway
, 1996
"... The extravasation ofleukocytes from the blood into tissues occurs as a multistep process: an initial transient interaction ("rolling"), generally thought to be mediated by the selectin family of adhesion molecules, followed by firm adhesion, usually mediated by integrins. Using a parallel ..."
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Cited by 26 (2 self)
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The extravasation ofleukocytes from the blood into tissues occurs as a multistep process: an initial transient interaction ("rolling"), generally thought to be mediated by the selectin family of adhesion molecules, followed by firm adhesion, usually mediated by integrins. Using a parallel plate flow chamber designed to approximate physiologic flow in postcapiUary venules, we have characterized a rolling interaction between lymphoid cells and adherent primary and cultured endothelial cells that is not selectin mediated. Studies using blocking monoclonal antibodies indicate that this novel interaction is mediated by CD44. Abrogation of the rolling interaction could he specifically achieved using both soluble hyaluronate (HA) and treatment of the adherent cells with HA-reactive substances, indicating that HA is the ligand supporting this rolling interaction. Some B and T cell hnes, as well as normal lymphocytes, either constitutively exhibit rolling or can be induced to do so by phorbol ester or in vivo antigen activation. These studies indicate that CD44 and its principal ligand hyaluronate represent another receptor/carbohydrate hgand pair mediating a novel activation-dependent pathway of lymphocyte/endothelial cell adhesion, T
CB: Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody
- J Clin Invest
, 1995
"... The role of the chemokine, macrophage inflammatory pro-tein-2 (MIP-2), during anti-glomerular basement mem-brane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Re-combinant rat MIP-2 (rMIP-2) from Escherichia coli exhib-ited neutrophil chemotactic ..."
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Cited by 26 (5 self)
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The role of the chemokine, macrophage inflammatory pro-tein-2 (MIP-2), during anti-glomerular basement mem-brane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Re-combinant rat MIP-2 (rMIP-2) from Escherichia coli exhib-ited neutrophil chemotactic activity and produced neutro-phil influx when injected into the rat bladder wall. By using a riboprobe derived from the cDNA and an anti-rMIP-2 polyclonal Ab, MIP-2 was found to be induced in glomeruli with anti-GBM Ab GN as mRNA by 30 min and protein by 4 h, with both disappearing by 24 h. The expression of MIP-2 correlated with glomerular neutrophil influx. A single dose of the anti-MIP-2 Ab 30 min before anti-GBM Ab was effective in reducing neutrophil influx (40 % at 4 h, P < 0.01) and periodic acid-Schiff deposits containing fibrin (54 % at 24 h, P < 0.01). The anti-rMIP-2 Ab had no effect on anti-GBM Ab binding (paired-label isotope study). Functional improvement in the glomerular damage was evi-denced by a reduction of abnormal proteinuria (P < 0.05). These results suggest that MIP-2 is a major neutrophil chemoattractant contributing to influx of neutrophils in Ab-induced glomerular inflammation in the rat. (J. Clin. Invest. 1995. 95:1009-1017.) Key words: macrophage inflamma-tory protein-2 * anti-glomerular basement membrane glo-merulonephritis * anti-macrophage inflammatory protein-2 antibody * neutrophils * chemokine
