Abstract
Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is an integral component of endothelial cells and has been implicated in the transendothelial migration (TEM) of circulating leukocytes mediated by its 1st and 2nd extracellular immunoglobulin (Ig)-like domains and regulation of intracellular Ca2+ homeostasis with its 6th domain. Up-to-date, little is known about the role of the 5th extracellular (Ig)-like domain. We have discovered a novel human PECAM-1 transcript missing the entire 7th exon, which encodes the 5th extracellular (Ig)-like domain of PECAM-1. A synthetic peptide with sequence homology to the 5th domain of PECAM-1 (JHS-7 peptide) and a corresponding polyclonal antibody (JHS-7 Ab) were prepared and their potential role in transendothelial migration and Ca2+ influx was measured. The JHS-7 peptide and the antibody exerted a dose dependent decrease (50-80%) in the transendothelial migration of freshly isolated human monocytes and a promonocytic cell line (U-937) in resting HUVECs and HUVECs activated with tumor necrosis factor-α. This was accompanied by an increase in Ca2+ influx and decrease in refilling of the intracellular Ca2+ stores in HUVECs. In summary, we have identified a novel PECAM-1 transcript (Δexon 7) and shown that the 5th (Ig)-like domain of PECAM-1 plays a role in monocyte TEM and Ca2+ homeostasis.
Original language | English (US) |
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Pages (from-to) | 1228-1235 |
Number of pages | 8 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 320 |
Issue number | 4 |
DOIs | |
State | Published - Aug 6 2004 |
Keywords
- Atherosclerosis
- Ca
- Endothelial cell
- PECAM-1
- Transmigration
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology