Cooperation between secretory phospholipase A2 and TNF-receptor superfamily signaling: implications for the inflammatory response in atherogenesis.
Atherogenesis is the consequence of a variety of effector mechanisms rather than the result of a single functional molecule. In this connection, type IIA secretory phospholipase A2 (sPLA2) is an acute-phase reactant, which accumulates in atherosclerotic arterial walls, elicits several effects on monocytes, and has been related to the development of atherosclerosis. CD40/CD40 ligand pair is also a strong proatherogenic system. sPLA2 produced an increase of the surface expression of CD40 in THP-1 monocytes and enhanced the effect of CD40 ligation on the expression of both Fas and FasL, thus indicating the existence of a positive cooperation between sPLA2 and different elements of the TNF-receptor superfamily. Activation of the CD40/CD40L dyad with anti-CD40 antibody produced a small release of arachidonic acid and lacked any significant effect on the induction of cyclooxygenase-2, whereas the secretion of the chemokine MCP-1 and the surface display of CD11b, the alpha chain of the integrin Mac-1, were upregulated. Engagement of CD40 did not influence the survival of THP-1 monocytes, but coincubation of THP-1 monocytes pretreated with anti-CD40 antibody and Jurkat cells induced a significant increase of the number of Jurkat cells showing binding of annexin-V, and nuclear condensation and fragmentation, thus indicating that this treatment might trigger a juxtacrine/paracrine mechanism of apoptotic death in sensitive cell types. This data indicates the existence of overlapping routes for the response to CD40, TNF-alpha, and sPLA2, thus allowing the development of distinct patterns of response in monocytic cells.
Fuentes
Lucía
L
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Facultad de Medicina, Valladolid, Spain.
Hernández
Marita
M
Fernández-Avilés
Francisco Jesús
FJ
Crespo
Mariano Sánchez
MS
Nieto
María Luisa
ML
D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D001161:Arteriosclerosis / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D054501:Group II Phospholipases A2; D006801:Humans; D007249:Inflammation / Q000276:immunology; D019169:Jurkat Cells; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism
D019013:CD40 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D023201:CD40 Ligand; D016718:Arachidonic Acid; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2