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Lipoxygenase metabolites induced expression of adhesion molecules and transendothelial migration of monocyte‐like HL‐60 cells is linked to protein kinase C activation
Author(s) -
Sultana Chand,
Shen Yamin,
Rattan Vinod,
Kalra Vijay K.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199606)167:3<477::aid-jcp12>3.0.co;2-1
Subject(s) - microbiology and biotechnology , monocyte , chemistry , kinase , protein kinase c , protein kinase a , lipoxygenase , protein expression , adhesion , cell adhesion molecule , biochemistry , enzyme , biology , immunology , gene , organic chemistry
Studies have shown that, among lipoxygenase metabolites examined, 15(S)‐hydroperoxy‐5,8,11,13‐eicosa‐tetraenoic acid (15[S]‐HPETE), at micromolar concentrations, selectively causes injury to cultured endothelial cells. We investigated whether physiologically relevant concentrations of lipoxygenase metabolites affected the expression of cell adhesion molecules (CAMs) involved in the adhesion of leukocytes and/or the accumulation of leukocytes in the vascular endothelium, these being the initial events in endothelial cell injury. Among lipoxygenase metabolites, 15(S)‐HPETE and 12(S)‐HETE, at nanomolar concentrations, induced surface expression of a subset of cell adhesion molecules (CAM), ICAM‐1, ELAM‐1, and VCAM‐1, in human umbilical vein endothelial cells (HUVEC), which is associated with an increased binding activity of the transcription factor, NF‐κB, to the consensus motif common to the CAM genes in the HUVEC nuclear extracts. Furthermore, 15(S)‐HPETE (1 nM) caused a threefold increase in the rate of transendothelial migration of vitamin D 3 ‐differentiated HL‐60 monocyte‐like cells and showed a thirtyfold increase in the phosphorylation of PECAM‐1, an adhesion molecule involved in endothelial cell‐cell adhesion. Both an antibody to PECAM‐1 and the protein kinase C inhibitor, GF 109203X, reduced 15(S)‐HPETE‐induced transmigration of monocyte‐like HL‐60 cells by approximately 75% and 85%, respectively. Treatment of HUVEC with a phosphatase inhibitor, calyculin A, augmented both the phosphorylation of PECAM‐1 and transmigration of monocyte‐like HL‐60 cells induced by 15(S)‐HPETE. Our results show that 15(S)‐HPETE, at physiological concentrations, induced activation of protein kinase C in HUVEC and leads to the phosphorylation of PECAM‐1, thus facilitating the migration of monocyte‐like HL‐60 cells across the endothelial cell monolayer. It is suggested that phosphorylation/dephosphorylation events in PECAM‐1 are important in regulating the trafficking of monocytes across the endothelial cell monolayer. © 1996 Wiley‐Liss, Inc.