beta1 and beta2 integrins activate different signalling pathways in monocytes.
Integrin-mediated signals play an important but poorly understood role in regulating many leucocyte functions. In monocytes and macrophages, integrins of the beta2 subfamily are involved in cell-cell interactions that are important for migration of the cells through the endothelium and also for phagocytosis. On the other hand, in the same cells, beta1 integrin-mediated adhesion to extracellular matrix proteins results in a strong induction of immediate early genes that are important in inflammation. To investigate the signalling pathways from these two types of integrin in monocytic cells, THP-1 cells were selectively stimulated via beta1 or beta2 integrins by cross-linking each type of receptor with specific monoclonal antibodies or their natural ligands. The involvement of extracellular signal-regulated kinase (ERK), Syk and phosphoinositide 3-kinase (PI-3K) was then analysed. Nuclear factor kappaB (NF-kappaB) activation was also detected in THP-1 cells transiently transfected with an NF-kappaB-driven luciferase reporter gene. We found that binding of both types of integrin to their natural ligands activated ERK in a Syk- and PI-3K-dependent manner. Yet, cross-linking of integrins by anti-beta1 antibodies caused activation of ERK while that by anti-beta2 antibodies did not. Also both types of integrin activated NF-kappaB. However, PI-3K was required for beta1 integrin-, but not beta2 integrin-, mediated NF-kappaB activation. In addition, inhibition of PI-3K with wortmannin and LY294002 blocked beta1 integrin-mediated NF-kappaB activation, but did not affect that mediated by beta2 integrin. These data suggest that distinct integrins activate different signalling pathways in monocytic cells.
Reyes-Reyes
Merit
M
Departamento de Inmunología, Instituto de Investigaciones Biomédicas UNAM, Apto. Postal 70228, Cd. Universitaria, México D.F. 04510, Mexico.
Mora
Nancy
N
Gonzalez
Gerardo
G
Rosales
Carlos
C
D000730:Androstadienes / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D002867:Chromones; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D000072377:Syk Kinase; D014443:Tyrosine; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C000606896:SYK protein, human