Facilitatory interplay in alpha 1a and beta 2 adrenoceptor function reveals a non-Gq signaling mode: implications for diversification of intracellular signal transduction.

Agonist occupied alpha(1)-adrenoceptors (alpha(1)-ARs) engage several signaling pathways, including phosphatidylinositol hydrolysis, calcium mobilization, arachidonic acid release, mitogen-activated protein (MAP) kinase activation, and cAMP accumulation. The natural agonist norepinephrine (NE) activates with variable affinity and intrinsic efficacy all adrenoceptors, and in cells that coexpress alpha(1)- and beta-AR subtypes, such as cardiomyocytes, this leads to coactivation of multiple downstream pathways. This may result in pathway cross-talk with significant consequences to heart physiology and pathologic state.

Failed efficacy of soluble human CD83-Ig in allogeneic mixed lymphocyte reactions and experimental autoimmune encephalomyelitis: implications for a lack of therapeutic potential.

Soluble forms of CD83, a dendritic cell-specific surface glycoprotein, have been strongly proposed to be of therapeutic utility in inflammatory conditions such as multiple sclerosis and transplantation. We demonstrate here, however, that eukaryotically expressed, recombinant soluble human CD83-Ig molecules fail to achieve efficacy in model systems for those conditions: mouse experimental autoimmune encephalomyelitis models in vivo or in mixed lymphocyte reactions in vitro. These results raise concern as to the viability of a eukaryotically expressed soluble CD83 strategy for clinical therapeutic use.

WITHDRAWN: Failed efficacy of soluble human CD83-Ig in allogeneic mixed lymphocyte reactions and experimental autoimmune encephalomyelitis: implications for a lack of therapeutic potential?

This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).