Outer membrane protein A of Escherichia coli K1 selectively enhances the expression of intercellular adhesion molecule-1 in brain microvascular endothelial cells.
Escherichia coli K1 meningitis is a serious central nervous system disease with unchanged mortality and morbidity rates for last few decades. Intercellular adhesion molecule 1 (ICAM-1) is a cell adhesion molecule involved in leukocyte trafficking toward inflammatory stimuli at the vascular endothelium; however, the effect of E. coli invasion of endothelial cells on the expression of ICAM-1 is not known. We demonstrate here that E. coli K1 invasion of human brain microvascular endothelial cells (HBMEC) selectively up-regulates the expression of ICAM-1, which occurs only in HBMEC invaded by the bacteria. The interaction of outer membrane protein A (OmpA) of E. coli with its receptor, Ecgp, on HBMEC was critical for the up-regulation of ICAM-1 and was depend on PKC-alpha and PI3-kinase signaling. Of note, the E. coli-induced up-regulation of ICAM-1 was not due to the cytokines secreted by HBMEC upon bacterial infection. Activation of NF-kappaB was required for E. coli mediated expression of ICAM-1, which was significantly inhibited by over-expressing the dominant negative forms of PKC-alpha and p85 subunit of PI3-kinase. The increased expression of ICAM-1 also enhanced the binding of THP-1 cells to HBMEC. Taken together, these data suggest that localized increase in ICAM-1 expression in HBMEC invaded by E. coli requires a novel interaction between OmpA and its receptor, Ecgp.
Selvaraj
Suresh K
SK
Division of Infectious Diseases, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Periandythevar
Parameswaran
P
Prasadarao
Nemani V
NV
D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology*; D001921:Brain / Q000166:cytology*; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*
D001425:Bacterial Outer Membrane Proteins; D018799:Intercellular Adhesion Molecule-1; C078167:OMPA outer membrane proteins