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

Montecucco, Fabrizio; Steffens, Sabine; Burger, Fabienne; Da Costa, Ana; Bianchi, Giordano; Bertolotto, Maria; Mach, François; Dallegri, Franco; Ottonello, Luciano

doi:10.1016/j.cellsig.2007.11.008

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Title		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
Authors		Montecucco, Fabrizio Steffens, Sabine Burger, Fabienne Da Costa, Ana Bianchi, Giordano Bertolotto, Maria Mach, François Dallegri, Franco Ottonello, Luciano show all authors [1 - 9]
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		DOI: 10.1016/j.cellsig.2007.11.008 PMID: 18164590
Full text		Article (Accepted version) (1.1 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
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