Secretion of Apolipoprotein E From Macrophages Occurs via a Protein Kinase A– and Calcium-Dependent Pathway Along the Microtubule Network

Publisher Website
Google Scholar
Abstract
Macrophage-specific expression of apolipoprotein (apo)E protects against atherosclerosis; however, the signaling and trafficking pathways regulating secretion of apoE are unknown. We investigated the roles of the actin skeleton, microtubules, protein kinase A (PKA) and calcium (Ca 2+ ) in regulating apoE secretion from macrophages. Disrupting microtubules with vinblastine or colchicine inhibited basal secretion of apoE substantially, whereas disruption of the actin skeleton had no effect. Structurally distinct inhibitors of PKA (H89, KT5720, inhibitory peptide PKI 14–22 ) all decreased basal secretion of apoE by between 50% to 80% ( P 2+ ] i ) with 1,2-bis(2-aminophenoxy)ethane- N , N , N ′, N ′-tetraacetate-acetoxymethyl ester (BAPTA-AM) inhibited apoE secretion by 77.2% ( P +/+ bone marrow–derived macrophages into the peritoneum of apoE −/− C57Bl6 mice resulted in time-dependent secretion of apoE into plasma, which was significantly inhibited by transient exposure of macrophages to BAPTA-AM and colchicine and less effectively inhibited by H89. We conclude that macrophage secretion of apoE occurs via a PKA- and calcium-dependent pathway along the microtubule network.