The leukocyte chemotactic receptor FPR1 (Formyl Peptide Receptor 1) is expressed on lens epithelial cells and regulates lens homeostasis

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NIAID	CELLBIO-21

Authors

• E Schneider
• S Gaur
• J Gao
• P Murphy

Abstract

FPR1 is a G protein-coupled chemoattractant receptor expressed mainly on leukocytes. Surprisingly, aging Fpr1-/- mice develop spontaneous lens degeneration without inflammation or infection. Since the lens contains only lens epithelial cells (LECs), we hypothesized that functional FPR1 is expressed directly on these cells. Both primary mouse LECs and the human LEC line FHL-124 expressed FPR1 mRNA. FHL-124 cells were strongly FPR1+ by Western blot and FACS, and the FPR1 agonist fMLF induced pertussis toxin-sensitive Ca2+ flux responses in these cells. The fluorescent FPR1 ligand fNLFNYK-Fl revealed ~3,000 specific binding sites with a KD~0.2 nM on FHL-124 cells as compared with ~50,000 sites on neutrophils and a KD~3 nM. Interestingly, three atypical FPR1 features were observed on FHL-124 cells as compared to neutrophils and FPR1-transfected HEK293 cells: 1) only a small percentage of FPR1 could be internalized by agonist stimulation, 2) most of the fNLFNYK-Fl binding sites were non-specific (confirmed by confocal microscopy), and 3) most of the immunoreactive receptor appeared as a 120 kDa complex, and a smaller component as the classic 60 kDa form. Thus, an atypical form of FPR1 is expressed directly by human LECs. Absence of LEC Fpr1 may account for lens degeneration in Fpr1-/- mice.

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