© 1996 American Heart Association, Inc.
Articles |
Lysophosphatidylcholine Promotes P-Selectin Expression in Platelets and Endothelial Cells
Possible Involvement of Protein Kinase C Activation and Its Inhibition by Nitric Oxide Donors
From the Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa.
Correspondence to Allan M. Lefer, PhD, Department of Physiology, Jefferson Medical College, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107-6799.
Abstract Lysophosphatidylcholine (LysoPC), an atherogenic lysophospholipid contained in oxidized low-density lipoprotein (LDL), has been shown to stimulate protein kinase C (PKC). Since PKC activators are suggested to elicit rapid P-selectin expression in platelets and endothelial cells, we examined whether LysoPC promotes P-selectin expression in platelets and P-selectin–mediated leukocyte adherence to endothelial cells via a mechanism involving PKC activation. LysoPC, but not phosphatidylcholine (PC), which is a major phospholipid component in native LDL, significantly upregulated P-selectin on cat platelets by flow cytometric analysis. This P-selectin upregulation by LysoPC was significantly attenuated by two PKC inhibitors, 7-hydroxystaurosporine (UCN-01) and N,N,N-trimethylsphingosine, and by two NO donors, CAS1609 and sodium nitroprusside. Submicellar concentrations of LysoPC significantly activated PKC in platelets, and this was inhibited by either UCN-01 or CAS1609. LysoPC, but not PC, significantly increased adherence of autologous cat polymorphonuclear leukocytes to coronary vascular endothelium, which was also markedly attenuated by UCN-01 and by CAS1609. LysoPC induced P-selectin expression on the surface of cat coronary vascular endothelium as assessed by immunohistochemical analysis. These results suggest that LysoPC, an atherogenic lysophospholipid contained in oxidized LDL, rapidly induces P-selectin expression in both platelets and endothelial cells at least partially via PKC activation. Furthermore, NO-generating agents may inhibit P-selectin upregulation by LysoPC. Since P-selectin may play an important role in initiating atherosclerosis, our data provide further insight into the mechanism of early stages of atherogenesis and of NO-mediated inhibition of atherosclerosis.
Key Words: flow cytometry • cell adhesion molecules • platelets • leukocyte adherence • endothelium
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