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Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils.
Proc Natl Acad Sci U S A. 1999 Oct 12; 96(21):12010-5.PN

Abstract

We previously have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified low density lipoprotein (MM-LDL), activates endothelial cells to bind monocytes. 1-Palmitoyl-2- (5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC) and 1- palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine (PGPC), which are present in OxPAPC, MM-LDL, and atherosclerotic lesions, were shown to have a major role in the activation of endothelial cells. We now demonstrate that these two highly similar molecules have dramatically different effects on leukocyte endothelial interactions. POVPC is a potent regulator of monocyte-specific endothelial interactions. Treatment of endothelial cells with POVPC increased monocyte binding by inducing the surface expression of the connecting segment 1 domain of fibronectin; no increase in neutrophil binding was observed. In addition, POVPC strongly inhibited lipopolysaccharide-mediated induction of neutrophil binding and expression of E-selectin protein and mRNA. This inhibition was mediated by a protein kinase A-dependent pathway, resulting in down-regulation of NF-kappaB-dependent transcription. In contrast, PGPC induced both monocyte and neutrophil binding and expression of E-selectin and vascular cell adhesion molecule 1. We present evidence to suggest that the two phospholipids act by different novel receptors present in Xenopus laevis oocytes and that POVPC, but not PGPC, stimulates a cAMP-mediated pathway. At concentrations equal to that present in MM-LDL, the effect of POVPC dominates and inhibits PGPC-induced neutrophil binding and E-selectin expression in endothelial cells. In summary, our data provide evidence that both POVPC and PGPC are important regulators of leukocyte-endothelial interactions and that POVPC may play a dominant role in a number of chronic inflammatory processes where oxidized phospholipids are known to be present.

Authors+Show Affiliations

Department of Medicine, University of California, Los Angeles, CA 90095-1679, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10518567

Citation

Leitinger, N, et al. "Structurally Similar Oxidized Phospholipids Differentially Regulate Endothelial Binding of Monocytes and Neutrophils." Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 21, 1999, pp. 12010-5.
Leitinger N, Tyner TR, Oslund L, et al. Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proc Natl Acad Sci U S A. 1999;96(21):12010-5.
Leitinger, N., Tyner, T. R., Oslund, L., Rizza, C., Subbanagounder, G., Lee, H., Shih, P. T., Mackman, N., Tigyi, G., Territo, M. C., Berliner, J. A., & Vora, D. K. (1999). Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proceedings of the National Academy of Sciences of the United States of America, 96(21), 12010-5.
Leitinger N, et al. Structurally Similar Oxidized Phospholipids Differentially Regulate Endothelial Binding of Monocytes and Neutrophils. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12010-5. PubMed PMID: 10518567.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. AU - Leitinger,N, AU - Tyner,T R, AU - Oslund,L, AU - Rizza,C, AU - Subbanagounder,G, AU - Lee,H, AU - Shih,P T, AU - Mackman,N, AU - Tigyi,G, AU - Territo,M C, AU - Berliner,J A, AU - Vora,D K, PY - 1999/10/16/pubmed PY - 1999/10/16/medline PY - 1999/10/16/entrez SP - 12010 EP - 5 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 96 IS - 21 N2 - We previously have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified low density lipoprotein (MM-LDL), activates endothelial cells to bind monocytes. 1-Palmitoyl-2- (5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC) and 1- palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine (PGPC), which are present in OxPAPC, MM-LDL, and atherosclerotic lesions, were shown to have a major role in the activation of endothelial cells. We now demonstrate that these two highly similar molecules have dramatically different effects on leukocyte endothelial interactions. POVPC is a potent regulator of monocyte-specific endothelial interactions. Treatment of endothelial cells with POVPC increased monocyte binding by inducing the surface expression of the connecting segment 1 domain of fibronectin; no increase in neutrophil binding was observed. In addition, POVPC strongly inhibited lipopolysaccharide-mediated induction of neutrophil binding and expression of E-selectin protein and mRNA. This inhibition was mediated by a protein kinase A-dependent pathway, resulting in down-regulation of NF-kappaB-dependent transcription. In contrast, PGPC induced both monocyte and neutrophil binding and expression of E-selectin and vascular cell adhesion molecule 1. We present evidence to suggest that the two phospholipids act by different novel receptors present in Xenopus laevis oocytes and that POVPC, but not PGPC, stimulates a cAMP-mediated pathway. At concentrations equal to that present in MM-LDL, the effect of POVPC dominates and inhibits PGPC-induced neutrophil binding and E-selectin expression in endothelial cells. In summary, our data provide evidence that both POVPC and PGPC are important regulators of leukocyte-endothelial interactions and that POVPC may play a dominant role in a number of chronic inflammatory processes where oxidized phospholipids are known to be present. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/10518567/Structurally_similar_oxidized_phospholipids_differentially_regulate_endothelial_binding_of_monocytes_and_neutrophils_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10518567 DB - PRIME DP - Unbound Medicine ER -