Inhibitory control of TGF‐β1 on the activation of Rap1, CD11b, and transendothelial migration of leukocytes
| Autor: | Derek Davies, IJsbrand M. Kramer, Mauro Perretti, Andrew Grimshaw, Caroline Basoni, Muriel Nobles, Elisabeth Génot, Claude Desgranges |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Integrins Chemokine Integrin alpha4 medicine.medical_treatment Integrin Lipopolysaccharide Receptors Inflammation Biology Transfection Biochemistry Monocytes Transforming Growth Factor beta1 Cell Movement Transforming Growth Factor beta Cell Adhesion Leukocytes Genetics medicine Guanine Nucleotide Exchange Factors Humans RNA Messenger Chemokine CCL4 Cell adhesion Molecular Biology Fluorescent Dyes Rose Bengal CD11b Antigen U937 cell Cell adhesion molecule Endothelial Cells rap1 GTP-Binding Proteins Cell Differentiation U937 Cells Macrophage Inflammatory Proteins Flow Cytometry Cell biology Enzyme Activation Cytokine Integrin alpha M biology.protein Tetradecanoylphorbol Acetate medicine.symptom Biotechnology |
| Zdroj: | The FASEB Journal. 19:1-25 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | Beta2-integrins are a family of dimeric adhesion molecules expressed on leukocytes. Their capacity to bind ligand is regulated by their state of activation. CD11b, an alphaMbeta2 integrin, is implicated in a number of physiological and pathological events such as inflammation, thrombosis, or atherosclerosis. The GTPase Rap1 is essential for its activation and could therefore play a strategic role in the regulation of leukocyte functioning. Because low levels of circulating TGF-beta have been linked with severe atherosclerosis, we have assessed the role of this cytokine in the regulation of Rap1 and CD11b activation in differentiated U937 cells and in human peripheral blood monocytes. TGF-beta1 caused a significant reduction in the expression of CD11b but not in the expression of other integrins tested. More importantly, TGF-beta1 greatly reduced the capacity of PMA or chemokines to activate CD11b and Rap1, a phenomenon paralleled by a loss of the Epac transcript and a reduction in 8-pCPT-2'-O-Me-cAMP-mediated activation of Rap1. This inhibition diminished the capacity of monocytes to migrate across a monolayer of endothelial cells. The inhibitory effect of TGF-beta1 on Rap1 activity may exert a general protective influence against aberrant transendothelial migration, thereby holding inflammatory responses in check. |
| Databáze: | OpenAIRE |
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