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Tumor necrosis factor-alpha (TNF-alpha) induces integrin CD11b/CD18 (Mac-1) up-regulation and migration to the CC chemokine CCL3 (MIP-1alpha) on human neutrophils through defined signalling pathways |
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Published in | Cellular signalling. 2008, vol. 20, no. 3, p. 557-68 | |
Abstract | Strong evidence suggests that neutrophils may play an active role in acute and chronic inflammatory disorders, such as rheumatoid arthritis and atherosclerosis. Given the role of pro-inflammatory cytokine TNF-alpha in these inflammatory processes, we planned the present study to investigate the effect of short term incubation with TNF-alpha on neutrophil migration to CCL3, a chemokine produced in inflammatory sites and normally devoid of neutrophil chemotactic properties. We found that TNF-alpha primed neutrophils for migration to CCL3 via CCR5. TNF-alpha-induced migration was a consequence of the TNF-alpha-induced up-regulation of integrin CD11b/CD18 (Mac-1) on neutrophil surface. Furthermore, TNF-alpha activity was found to be strictly dependent on the activation of ERK 1/2 p44, cooperating with the intracellular pathways involving Src kinases, PI3K/Akt, p38 MAPK, well known as activated in response to classical chemoattractants (CXCL8) or priming agents (GM-CSF). On the contrary, the effect of TNF-alpha on neutrophil migration to CCL3 was not dependent on JNK 1/2. In conclusion, the present report shows that TNF-alpha unveils a previously unknown capacity of neutrophils to migrate to CCL3 through the intervention of Mac-1. TNF-alpha regulates Mac-1 up-regulation through signalling pathways, involving various kinases, but not JNK 1/2. Although highly speculative, ERK 1/2 p44 may represent a selective target for the pharmacologic manipulation of neutrophil-mediated adverse activities in TNF-alpha-mediated inflammatory states. | |
Keywords | 1-Phosphatidylinositol 3-Kinase/metabolism — Adult — Antigens, CD11b/metabolism — Antigens, CD18/metabolism — Chemokine CCL3/metabolism — Chemotaxis, Leukocyte — Humans — Inflammation/immunology/metabolism — Macrophage-1 Antigen/metabolism — Middle Aged — Mitogen-Activated Protein Kinase 1/metabolism — Mitogen-Activated Protein Kinase 3/metabolism — Neutrophil Activation — Neutrophils/enzymology/immunology/metabolism — Proto-Oncogene Proteins c-akt/metabolism — Receptors, CCR5/metabolism — Recombinant Proteins/metabolism — Signal Transduction — Tumor Necrosis Factor-alpha/metabolism — Up-Regulation — P38 Mitogen-Activated Protein Kinases/metabolism — Src-Family Kinases/metabolism | |
Identifiers | PMID: 18164590 | |
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Research groups | Biologie du myocarde (22) L'athérosclérose et ses complications cliniques (591) Le rôle du système endocannabinoïde dans l'athérosclérose (882) | |
Citation (ISO format) | MONTECUCCO, Fabrizio et al. Tumor necrosis factor-alpha (TNF-alpha) induces integrin CD11b/CD18 (Mac-1) up-regulation and migration to the CC chemokine CCL3 (MIP-1alpha) on human neutrophils through defined signalling pathways. In: Cellular signalling, 2008, vol. 20, n° 3, p. 557-68. doi: 10.1016/j.cellsig.2007.11.008 https://archive-ouverte.unige.ch/unige:2143 |