Ligation of CD11b and CD11c β2 integrins by antibodies or soluble CD23 induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β production in primary human monocytes through a pathway dependent on nuclear factor–κB
| Autor: | Jean-Michel Dayer, Roger Rezzonico, Véronique Imbert, R Chicheportiche |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Proteasome Endopeptidase Complex
Chemokine Blotting Western Immunology Integrin CD11c Biology Biochemistry Antibodies Monocytes Multienzyme Complexes medicine Humans RNA Messenger Chemokine CCL4 Macrophage inflammatory protein Chemokine CCL3 CD11 Antigens Receptors IgE Cell adhesion molecule Interleukin-8 NF-kappa B Antibodies Monoclonal Cell Biology Hematology Macrophage Inflammatory Proteins Fusion protein Molecular biology Cysteine Endopeptidases Solubility Integrin alpha M CD18 Antigens Proteasome inhibitor biology.protein medicine.drug |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v97.10.2932 |
| Popis: | Chemokines and adhesion molecules such as integrins play a major part in the trafficking, extravasation, and recruitment of leukocytes to inflammatory sites. This study investigated the effects of beta(2) integrin engagement on chemokine production by freshly isolated human monocytes. We found that ligation of CD11b or CD11c but not CD11a alpha chains of beta(2) integrins by antibodies or soluble CD23 (sCD23) fusion proteins rapidly induced transcription and secretion of interleukin 8, macrophage inflammatory protein (MIP) 1alpha, and MIP-1beta. Because the promoters of these chemokine genes contain kappaB binding sites, we assessed the possible role of nuclear factor-kappaB (NF-kappaB) in controlling induction of the genes through beta(2) integrin engagement. Electrophoretic mobility shift assays showed that sCD23 or antibodies to CD11b or to CD11c up-regulated DNA-binding activity of NF-kappaB. Activation of NF-kappaB was accompanied by degradation of its cytosolic inhibitor IkappaB-alpha. Blockade of depletion of IkappaB-alpha by proteasome inhibitors (proteasome inhibitor I or acetyl-leucinyl-leucinyl-norleucinal) led to concomitant inhibition of NF-kappaB DNA-binding activity and expression of MIP-1alpha and MIP-1beta messenger RNA induced by beta(2) integrin ligation. These results suggest that triggering of CD11b or CD11c beta(2) integrin on primary human monocytes provides activation signals leading to nuclear translocation of NF-kappaB and subsequent secretion of MIP-1alpha and MIP-1beta that may have an important role in recruitment of other inflammatory cells during initiation of an inflammatory response. |
| Databáze: | OpenAIRE |
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