Modulating Influence of Chemotactic Factor-Induced Cell Adhesiveness on Granulocyte Function

Fehr, Jörg; Dahinden, Clemens A.

doi:10.1172/jci109466

Cited by 139 publications

(70 citation statements)

References 30 publications

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“…After isolation, neutrophils were resuspended at a final concentration of 2 x 10' cells/ml in PBS. The leukocyte adhesion assay was a modification of the method of Fehr and Dahinden (33). Briefly, leukocytes were radiolabeled by incubating purified feline neutrophils (2 x 107 cell/ml) with 30 pCi/ml of Na5"CrO4 at 370C for 60 min.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion.

Kubes¹,

Jutila²,

Payne³

1995

J. Clin. Invest.

242

147

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Leukocyte rolling has been postulated to be mandatory for subsequent leukocyte adhesion and tissue injury observed during ischemia/reperfusion. The objective of this study was to systematically assess this hypothesis at the microvascular level by examining the effects of various concentrations of a selectin-binding carbohydrate (fucoidin) on the increased rolling and adhesion of leukocytes in postischemic venules. The contribution of L-selectin and/or P-selectin to leukocyte rolling were also assessed in this model. Using intravital microscopy we observed that 60 min of ischemia followed by reperfusion caused a profound increase in leukocyte rolling and adhesion. A high dose of fucoidin (25 mg/kg) reduced leukocyte rolling by > 90% and significantly reduced leukocyte adhesion, whereas a lower dose of fucoidin still reduced leukocyte rolling by 60% but had no effect on leukocyte adhesion. Moreover, despite the profound reduction in leukocyte rolling with fucoidin, the remaining rolling cells were able to firmly adhere via a CD18-dependent mechanism, particularly in those postcapillary venules with reduced (30-50%) shear rates. The increased rolling was also reduced 60% by either an anti-P-selectin antibody, an anti-L-selectin antibody, or a combination of the two antibodies, but this reduction in rolling cells did not translate into significantly reduced leukocyte adhesion. Our data suggest that L-selectin, P-selectin, and a fucoidin-sensitive pathway contribute to the significant increase in reperfusion-induced leukocyte rolling. However, targeting leukocyte rolling as a form of therapy requires very significant efficacy (> 90%) to achieve reasonable (-50%) attenuation in leukocyte adhesion in postischemic venules. (J. Clin. Invest. 1995Invest. . 95:2510Invest. -2519

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Section: Methodsmentioning

confidence: 99%

Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion.

Kubes¹,

Jutila²,

Payne³

1995

J. Clin. Invest.

242

147

View full text Add to dashboard Cite

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“…The time-dependent loss of responsiveness to cyt B (desensitization to cyt B) do not imply a general functional hypo-responsiveness of FMP-pretreated PMN, since the same cells release remarkable O,-in response to con A or WGA. Therefore, these cells are rather activated [9,17]. It is possible that the same metabolic events induced by FMP may be responsible not only for the increased responsiveness to con A or WGA but also for the decreased responsiveness to cyt B.…”

Section: Resultsmentioning

confidence: 99%

Effect of the chemotactic peptide on the subsequent superoxide releasing response in human polymorphonuclear leukocytes

Kitagawa

Takaku

1981

FEBS Letters

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“…While the mechanism of the benoxaprofen-induced decrease in chemotactic responsiveness of mononuclear phagocytes has not been elucidated, it clearly is not associated with an increase in leukocyte adherence (Table 1). In contrast, such increases in leukocyte adherence may account in part for the inhibition of neutrophil chemotaxis both by benoxaprofen (Table I) and by prior exposure of neutrophils to maximally deactivating concentrations of some chemotactic factors (7).…”

Section: Discussionmentioning

confidence: 99%

Selective immobilization of human mononuclear phagocytes by benoxaprofen

Goetzl

Valone

1982

Arthritis & Rheumatism

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Benoxaprofen [2-(4-chlorophenyl)-cu-methyl-5-benzoxazoleacetic acid] is a potent antiinflammatory agent that effectively suppresses edema and the infiltration of leukocytes in animal models of acute and chronic inflammation (1,2). Benoxaprofen has prevented the development of adjuvant arthritis in rats and reduced the intensity of established lesions of 14-25 days duration (1). The influx of mononuclear leukocytes into the pleural cavity of rats in response to injections of dextran or carrageenan was inhibited to a greater extent than that of polymorphonuclear neutrophi1 leukocytes (PMNs) (2). That the migration of rat, guinea pig, and human mononuclear leukocytes is more susceptible to inhibition by benoxaprofen than the migration of PMNs, was confirmed in vitro by both glass capillary tube and Boyden chamber techniques (2-4). The results of the present study indicate that concentrations of benoxaprofen achieved routinely in humans by a standard anti-arthritis regimen suppress the enhanced migration of human monocytes and macrophages exposed to different stimuli significantly more than that of human neutrophils and T lymphocytes. The inhibition of human mononuclear phagocyte chemotaxis by benoxaprofen is attributable to a direct and reversible immobilizing effect, while the increased adherence induced by higher concentrations of benoxaprofen may contribute to the suppression of neutrophil chemotaxis. MATERIALS AND METHODSWe obtained the following materials from the specified suppliers: Eagle's minimal essential medium, fetal bovine serum, and Hank's balanced salt solution (HBSS) (M.A. Bioproducts, Walkersville, MD); Sephadex G-10 and Sephadex G-25, macromolecular dextran (Macrodex), and Ficoll-Hypaque (Pharmacia Fine Chemicals, Inc., Piscataway, NJ); 5 times recrystallized ovalbumin and concanavalin A (Con A) (Miles Laboratories, Inc., Elkhart, IN); 3-p and 8-p pore membrane filters (Sartorius Filters, Hayward, CA); 8-p channel filters (Nuclepore Corp., Pleasanton, CA); N-formyl-methionyl-leucyl-phenylalanine (fMLP) and a-thioglycerol (Sigma Chemical Co., St. Louis, MO), and chemotactic chambers with a 0.2-ml blind-end stimulus compartment (Neuroprobe, Inc., Bethesda, MD). Chemotactic fragments of the fifth component of human complement (C5fr) and leukotriene B4 were prepared and purified as described (4). Benoxaprofen was supplied by Lilly Research Laboratories (Indianapolis, IN) and was solubilized in HBSS immediately before use by titration with 1M sodium hydroxide to provide a I-mg/ml stock solution (pH 7.2).Isolation of human leukocytes. Neutrophils, mixed mononuclear leukocytes, and T lymphocytes were obtained from sodium citrate-anticoagulated venous blood of normal subjects (5,6). Suspensions of mixed leukocytes in HBSS containing 0.2 gm of ovalbumin/100 ml and 0.00% Tris (hydroxymethyl) ami-

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Modulating Influence of Chemotactic Factor-Induced Cell Adhesiveness on Granulocyte Function

Cited by 139 publications

References 30 publications

Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion.

Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion.

Effect of the chemotactic peptide on the subsequent superoxide releasing response in human polymorphonuclear leukocytes

Selective immobilization of human mononuclear phagocytes by benoxaprofen

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