RT info:eu-repo/semantics/article T1 Cooperation between secretory phospholipase A2 and TNF-receptor superfamily signaling: Implications for the inflammatory response in atherogenesis A1 Fuentes, Lucía A1 Hernández Garrido, Marita A1 Fernández Avilés, Francisco Jesús A1 Sánchez Crespo, Mariano A1 Nieto Callejo, María Luisa K1 Cytokines K1 Citoquinas K1 Apoptosis K1 Atherosclerosis K1 Aterosclerosis K1 Lipid mediators K1 Mediadores lipídicos AB 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 α 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-α, and sPLA2, thus allowing the development of distinct patterns of response in monocytic cells. PB American Heart Association SN 0009-7330 YR 2002 FD 2002 LK https://uvadoc.uva.es/handle/10324/47010 UL https://uvadoc.uva.es/handle/10324/47010 LA eng NO Circulation Research, 2002, vol. 91, n. 8. p. 681-688 NO Producción Científica DS UVaDOC RD 27-dic-2024