MALEYLATED-BSA INDUCES HYDROLYSIS OF PIP2, FLUXES OF CA2-KAPPA-B BINDING, AND TRANSCRIPTION OF THE TNF-ALPHA GENE IN MURINE MACROPHAGES(, NF)

The interaction of altered lipids or proteins with the several scaveng er receptors (SR) on macrophages can lead to disparate results in both gene expression and cell function. However, the molecular bases of si gnaling induced by SR ligation have remained obscure, Here we report t hat maleylated-bovine serum albumin (maleyl-BSA) binds a low-affinity SR, initiating PIP2 hydrolysis, [Ca2+](i) spikes, phospholipase A(2) ( PLA(2)) activation, nuclear factor-kappa B (NF-kappa B) binding to its cognate nucleotide and tumor necrosis factor alpha (TNF-alpha) gene t ranscription, We recently reported that oxidized low-density lipoprote in (ox-LDL), which binds another macrophage SR, induced pertussis-toxi n-sensitive hydrolysis of PIP2 and elevations in [Ca2+](i) [J. Biol, C hem, 270, 3475-3478, 1995], By contrast, maleyl-BSA-initiated events w ere not pertussis toxin-sensitive and produced less [Ca2+](i) spiking than ox-LDL, Furthermore, maleyl-BSA led to binding of NF-kappa B to i ts cognate nucleotide and TNF-alpha gene transcription, whereas ox-LDL suppressed these events, Collectively, this data suggests that maleyl -BSA and ox-LDL bind to distinct SR on murine macrophages, initiate di stinct signal transduction pathways, and produce different functional effects.