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(Journal of Leukocyte Biology. 2001;70:677-683.)
© 2001 by Society for Leukocyte Biology

Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages

Uma K. Misra*, Charu L. Adlakha*, Govind Gawdi*, Michael K. McMillian{dagger}, Salvatore V. Pizzo* and Daniel T. Laskowitz{ddagger}

* Departments of Pathology,
{dagger} Pharmacology, and
{ddagger} Medicine (Neurology), Duke University Medical Center, Durham, North Carolina

Correspondence: Daniel Laskowitz, M.D., Department of Medicine (Neurology), Box 2900, Duke University Medical Center, Durham, NC 27710.

Apolipoprotein E (ApoE) is a 34-kDa cholesterol transport protein that also possesses immunomodulatory properties. In this study, we demonstrate that ApoE initiates a signaling cascade in murine peritoneal macrophages that leads to increased production of inositol triphosphate with mobilization of intracellular Ca2+ stores. This cascade is inhibited by pretreatment with receptor-associated protein and Ni2+, and it is mediated by a pertussis toxin-sensitive G protein. These properties are characteristic of signal transduction induced via ligand binding to the cellular receptor, lipoprotein receptor-related protein. A peptide derived from the receptor-binding region of ApoE also initiates signal transduction in a manner similar to that of the intact protein, suggesting that this isolated region is sufficient for signal transduction. The ApoE-mimetic peptide competed for binding with the intact protein, confirming that they both interact with the same site. ApoE-dependent signal transduction might play a role in mediating the functional properties of this lipoprotein.

Key Words: apolipoprotein E • receptor-associated protein • macrophage • lipoprotein receptor-related protein • signal transduction




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