Neuroprotectin D1/protectin D1 stereoselective and specific binding with human retinal pigment epithelial cells and neutrophils

Victor L. Marcheselli, Pranab K. Mukherjee, Makoto Arita, Song Hong, Rajee Antony, Kristopher Sheets, Jeremy W. Winkler, Nicos A. Petasis, Charles N. Serhan, Nicolas G. Bazan

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Abstract

Retinal pigment epithelial (RPE) cells, derived from the neuroectoderm, biosynthesize the novel lipid mediator neuroprotectin D1 (NPD1) from docosahexaenoic acid (DHA) in response to oxidative stress or to neurotrophins, and in turn, elicits cytoprotection. Here, we report the identification of a 16,17-epoxide-containing intermediate in the biosynthesis of NPD1 in ARPE-19 cells from 17S-hydro-(peroxy)-docosahexaenoic acid. We prepared and isolated tritium-labeled NPD1 ([3H]-NPD1) and demonstrate specific and high-affinity stereoselective binding to ARPE-19 cells (Kd=31.3±13.1 pmol/mg of cell protein). The stereospecific NPD1 interactions with these cells in turn gave potent protection against oxidative stress-induced apoptosis, and other structurally related compounds were weak competitors of NPD1 specific binding. This [3H]-NPD1/PD1 also displayed specific and selective high affinity binding with isolated human neutrophils (Kd∼25 nM). Neither resolvin E1 nor lipoxin A4 competed for [3H]-NPD1/PD1 specific binding with human neutrophils. Together, these results provide evidence for stereoselective specific binding of NPD1/PD1 with retinal pigment epithelial cells as well as human neutrophils. Moreover, they suggest specific receptors for this novel mediator in both the immune and visual systems.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume82
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1
Externally publishedYes

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Keywords

  • Binding
  • Inflammation
  • Mediators
  • Neuroprotectin
  • Photoreceptors
  • Resolution

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

Cite this

Marcheselli, V. L., Mukherjee, P. K., Arita, M., Hong, S., Antony, R., Sheets, K., Winkler, J. W., Petasis, N. A., Serhan, C. N., & Bazan, N. G. (2010). Neuroprotectin D1/protectin D1 stereoselective and specific binding with human retinal pigment epithelial cells and neutrophils. Prostaglandins Leukotrienes and Essential Fatty Acids, 82(1), 27-34. https://doi.org/10.1016/j.plefa.2009.10.010