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Title: Heparin attenuates TNF-alpha induced inflammatory response through a CD11b dependent mechanism
Author: Salas Martínez, Azucena
Sans i Cuffí, Miquel
Soriano Viladomiu, Alex
Reverter Calatayud, Juan Carlos
Anderson, D. C.
Piqué, J. M. (Piqué Badía)
Panés Díaz, Julià
Keywords: Heparina
Malalties inflamatòries intestinals
Inflammatory bowel diseases
Issue Date: 2000
Publisher: BMJ Group
Abstract: Background In addition to its anticoagulant properties, heparin has anti-inflammatory effects, the molecular and mechanistic bases of which are incompletely defined. AIMS The current studies were designed to test the hypothesis that heparin abrogates the expression or function of leucocyte-endothelial adherence molecules which are fundamental to the acute inflammatory response. Methods The effects of heparin on tumour necrosis factor alpha (TNF-¿) induced leucocyte rolling, adhesion, and migration as well as vascular permeability were assessed in rat mesenteric venules using intravital microscopy. Expression of adhesion molecules was quantitated using a double radiolabelled monoclonal antibody (mAb) binding technique in vivo (P-selectin, intercellular cell adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1)) or flow cytometry (CD11a, CD11b, and L-selectin). Ex vivo binding of heparin to neutrophils was assessed by flow cytometry. RESULTS TNF-alpha induced a significant increase in leucocyte rolling, adhesion, and migration, and vascular permeability, coincident with a significant increase in expression of P-selectin, ICAM-1, and VCAM-1. Ex vivo assessment of blood neutrophils showed significant upregulation of CD11a and CD11b and significant downregulation of L-selectin within five hours of TNF-¿ administration. Heparin pretreatment significantly attenuated leucocyte rolling, adhesion, and migration but did not affect expression of cell adhesion molecules or vascular permeability elicited by TNF-¿ administration. Binding of heparin was significantly increased on blood neutrophils obtained five hours after TNF-¿ administration. Preincubation with an anti-CD11b mAb but not with an anti-CD11a or anti-L-selectin antibody significantly diminished heparin binding ex vivo.
Note: Reproducció digital del document publicat a:
It is part of: Gut, 2000, vol. 47, núm 1, p. 88-96
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ISSN: 0017-5749
Appears in Collections:Articles publicats en revistes (Medicina)

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