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- Gillberg, L., et al.
(författare)
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Effective treatment of mouse experimental colitis by alpha 2 integrin antibody : comparison with alpha 4 antibody and conventional therapy
- 2013
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 207:2, s. 326-336
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Tidskriftsartikel (refereegranskat)abstract
- Aim To compare the therapeutic effect of a2 and a4 integrin-blocking antibodies to conventional inflammatory bowel disease drugs methotrexate, 5-aminosalicylic acid and azathioprine in the dextran sulphate sodium mouse colitis model. Methods Colitis was induced in balb/c mice with 2.53.0% dextran sulphate sodium. Treatment was given daily for 7 days after the onset of colitis, by rectal installation. Clinical signs of disease were assessed daily using a disease activity index. After 19 days, all animals were killed and colon samples collected for histological grading and mRNA/protein analysis. All treatment groups were compared with an untreated control group and a treatment group receiving dextran sulphate sodium alone to monitor the potential degree of clinical remission. Results Treatment with anti-a2 antibodies and methotrexate reduced the body weight loss. At the end of treatment, anti-a2 antibodies reduced rectal bleeding, while methotrexate reduced the disease activity index score. Histological evaluation showed that anti-a2 antibodies, methotrexate, 5-aminosalicylic acid and azathioprine treatment reduced the acute inflammation; methotrexate was the only treatment with effect on the crypt score. Compared with the dextran sulphate sodium alone group, the methotrexate group showed down-regulation of IL-1 beta at the mRNA level, while the anti-a2 antibody group displayed decreased protein expression of iNOS and IL-1 beta. Conclusions Specific blocking of extravascular trafficking of leucocytes with a2-antibodies could be a new beneficial drug target in inflammatory bowel disease.
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- Eriksson, EE, et al.
(författare)
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Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo
- 2001
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 194:2, s. 205-217
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Tidskriftsartikel (refereegranskat)abstract
- In the multistep process of leukocyte extravasation, the mechanisms by which leukocytes establish the initial contact with the endothelium are unclear. In parallel, there is a controversy regarding the role for L-selectin in leukocyte recruitment. Here, using intravital microscopy in the mouse, we investigated leukocyte capture from the free flow directly to the endothelium (primary capture), and capture mediated through interactions with rolling leukocytes (secondary capture) in venules, in cytokine-stimulated arterial vessels, and on atherosclerotic lesions in the aorta. Capture was more prominent in arterial vessels compared with venules. In venules, the incidence of capture increased with increasing vessel diameter and wall shear rate. Secondary capture required a minimum rolling leukocyte flux and contributed by ∼20–50% of total capture in all studied vessel types. In arteries, secondary capture induced formation of clusters and strings of rolling leukocytes. Function inhibition of L-selectin blocked secondary capture and thereby decreased the flux of rolling leukocytes in arterial vessels and in large (>45 μm in diameter), but not small (<45 μm), venules. These findings demonstrate the importance of leukocyte capture from the free flow in vivo. The different impact of blockage of secondary capture in venules of distinct diameter range, rolling flux, and wall shear rate provides explanations for the controversy regarding the role of L-selectin in various situations of leukocyte recruitment. What is more, secondary capture occurs on atherosclerotic lesions, a fact that provides the first evidence for roles of L-selectin in leukocyte accumulation in atherogenesis.
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- Sieweke, J, et al.
(författare)
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The cultural embeddedness of professional service purchasing : A comparative study of German and Swedish companies
- 2014
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Ingår i: Journal of Purchasing and Supply Management. - : Elsevier. - 1478-4092. ; 20:4, s. 273-285
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Tidskriftsartikel (refereegranskat)abstract
- Research on professional service purchasing generally takes a culturally universalistic approach, implicitly assuming the generalizability of research findings and normative models to different cultural contexts. However, research in related disciplines points to the influence of national culture on managers' decisions, thereby questioning the culturally universalistic approach. The purpose of this paper is to explore differences in professional service purchasing in different cultural contexts. Based on a survey of large organizations, we analyze how the purchasing process for a specific type of professional services - management consulting services - is organized in two cultural contexts (i.e. Germany and Sweden). The results indicate that organizations in Germany and Sweden differ in the way they approach key aspects of the purchasing process. These differences are discussed in relation to two central cultural dimensions - uncertainty avoidance and masculinity-femininity - in which Germany and Sweden take very different positions. It is proposed that uncertainty avoidance mainly influences the first steps in the purchasing process (specify, select and contract) whereas masculinity-femininity mainly influences the remaining steps (order, expedite and evaluate). The paper contributes to the purchasing and supply management literature by empirically illustrating differences in purchasing practices in different cultural contexts and developing theory-driven propositions for the influence of national culture on the professional service purchasing process.
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- Werr, Andreas, et al.
(författare)
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Constructing the legitimate buyer of management consulting services
- 2008
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Ingår i: Journal of Organizational Change Management. - : Emerald. - 0953-4814. ; 21:6, s. 758-772
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Hiring management consultants as external support in organizational change is in the literature described as a socially and emotionally stressful activity for managers. Management consultants need to deal with these threatening aspects of their service. This paper aims to explore the subject positions management consultants offer managers in their self‐presentations on the World Wide Web. Design/methodology/approach The paper studies the self‐presentations on the www of four large management consultancies–Accenture, BCG, KPMG, and McKinsey & Co. Using a Foucault inspired discourse analytical framework, we analyze the subject positions offered to client‐managers in these self‐presentations and how these subject positions relate to the management regimes of bureaucracy and post‐bureaucracy. Findings The study identifies two different discursive practices–one normalizing practice, constructing the use of management consultants as a natural aspect of management and a second practice rationalizing the use of management consultants, providing arguments aimed at reducing the pressures on the manager. The normalizing discourse which draws on a post‐bureaucratic regime was found in Accenture and KPMG. The rationalizing discourse was found in McKinsey and BCG and draws on the bureaucratic regime. Originality/value This work highlights how consultants deal with the pressures their presence puts on managers. It illustrates how managerial truth regimes contribute to shaping the conditions for management consulting and the consultant‐client relationship.
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- Werr, Andreas, et al.
(författare)
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The relationship between national culture and the use of professional services: Evidence from two cross-country studies
- 2018
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Ingår i: Journal of Purchasing and Supply Management. - : Elsevier. - 1478-4092. ; 24:4, s. 314-325
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Tidskriftsartikel (refereegranskat)abstract
- Each year, clients spend large sums on professional services, such as accounting services, legal services and consulting services. While research has found significant cross-country differences in organizations’ spending on professional services, we do not know why they occur. Inspired by the organizational buying behavior literature, this paper investigates the influence of national culture on the use of professional services, particularly management consulting services. As the use of professional services involves considerable uncertainties—particularly for the buyer—it can be assumed to be influenced by cultural differences regarding the level of Uncertainty Avoidance, Individualism and Masculinity. By drawing on two independent cross-country studies, we show that organizations in high uncertainty avoidance and individualistic cultures use professional services less than organizations in low uncertainty avoidance and collectivist cultures. We found no relationship between Hofstede's dimension of Masculinity and the use of professional services. The findings contribute to the theorizing on how the cultural context influences organizational buying behavior and the purchasing of professional services.
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- Werr, J, et al.
(författare)
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beta1 integrins are critically involved in neutrophil locomotion in extravascular tissue In vivo
- 1998
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 187:12, s. 2091-2096
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Tidskriftsartikel (refereegranskat)abstract
- Recruitment of leukocytes from blood to tissue in inflammation requires the function of specific cell surface adhesion molecules. The objective of this study was to identify adhesion molecules that are involved in polymorphonuclear leukocyte (PMN) locomotion in extravascular tissue in vivo. Extravasation and interstitial tissue migration of PMNs was induced in the rat mesentery by chemotactic stimulation with platelet-activating factor (PAF; 10−7 M). Intravital time-lapse videomicroscopy was used to analyze migration velocity of the activated PMNs, and the modulatory influence on locomotion of locally administered antibodies or peptides recognizing various integrin molecules was examined. Immunofluorescence flow cytometry revealed increased expression of α4, β1, and β2 integrins on extravasated PMNs compared with blood PMNs. Median migration velocity in response to PAF stimulation was 15.5 ± 4.5 μm/min (mean ± SD). Marked reduction (67 ± 7%) in motility was observed after treatment with mAb blocking β1 integrin function (VLA integrins), whereas there was little, although significant, reduction (22 ± 13%) with β2 integrin mAb. Antibodies or integrin-binding peptides recognizing α4β1, α5β1, or αvβ3 were ineffective in modulating migration velocity.Our data demonstrate that cell surface expression of β1 integrins, although limited on blood PMNs, is induced in extravasated PMNs, and that members of the β1 integrin family other than α4β1 and α5β1 are critically involved in the chemokinetic movement of PMNs in rat extravascular tissue in vivo.
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- Werr, J, et al.
(författare)
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Engagement of beta(2) integrins induces surface expression of beta(1) integrin receptors in human neutrophils
- 2002
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Ingår i: JOURNAL OF LEUKOCYTE BIOLOGY. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 68:4, s. 553-560
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Induction of β1 integrin (CD49/CD29) expression in polymorphonuclear leukocytes (PMN) has been shown to be associated with transendothelial migration recently. Yet, β1 integrin expression is relatively insensitive to cell activation with soluble agonists, such as N-formyl-methionyl-leucyl-phenylalanine (fMLP). We hypothesized that β2 integrins (CD11/CD18), critically involved in PMN adhesion and extravasation, may play a role in regulating β1 integrin expression in PMN. Antibody cross-linking of CD18, mimicking adhesion-dependent engagement of β2 integrins, resulted in rapid, tyrosine kinase-dependent upregulation of β1 integrins. This response was potentiated by simultaneous chemoattractant (fMLP) stimulation of PMN. Moreover, upregulation of β1 integrins evoked by CD18 cross-linking was found to support adhesion of fMLP-stimulated PMN to matrix proteins and also was critical for the ability of PMN to migrate in collagen gels in response to a gradient of fMLP. Taken together, these data demonstrate that engagement of β2 integrins in human PMN induces β1 integrin expression in these cells of significance for their migration in the extravascular tissue. Thus, β2 integrins may serve the function to regulate PMN locomotion in extravascular tissue via receptor crosstalk with β1 integrins.
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- Werr, J, et al.
(författare)
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Integrin alpha(2)beta(1) (VLA-2) is a principal receptor used by neutrophils for locomotion in extravascular tissue.
- 2000
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 95:5
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Tidskriftsartikel (refereegranskat)abstract
- Cell adhesion molecules are critically involved in the multistep process of leukocyte recruitment in inflammation. The specific receptors used by polymorphonuclear leukocytes (PMN) for locomotion in extravascular tissue have as yet not been identified. By means of immunofluorescence flow cytometry and laser scanning confocal microscopy, this study demonstrated that surface expression of the alpha(2)beta(1) (VLA-2) integrin, though absent on blood PMN, is induced in extravasated PMN collected from human skin blister chambers, and rat PMN accumulated in the peritoneal cavity after chemotactic stimulation. Intravital time-lapse videomicroscopy was used to investigate chemoattractant-induced PMN locomotion in the rat mesentery in vivo. Local administration of function-blocking monoclonal antibody or peptide recognizing the alpha(2)beta(1) integrin reduced PMN migration velocity in the extravascular tissue by 73% +/- 3% and 70% +/- 10%, respectively (means +/- SD). The distance f-met-leu-phe peptide (fMLP)-stimulated human PMN migrated in a collagen gel in vitro was markedly reduced by treatment with anti-alpha(2) mAbs or peptide, whereas no effect was observed with antibodies or peptides recognizing the alpha(4)beta(1) or alpha(5)beta(1) integrins. Further evidence for a critical role of expression of alpha(2)beta(1) integrin in PMN locomotion in extravascular tissue was obtained in the mouse air pouch model of acute inflammation where chemoattractant-induced PMN recruitment was substantially inhibited by local anti-alpha(2) mAb treatment. Thus, expression of alpha(2)beta(1) integrin on extravasated PMN has been identified and a novel role of this receptor in regulating the extravascular phase of leukocyte trafficking in inflammation has been formulated. (Blood. 2000;95:1804-1809)
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