Open AccessVEGF receptor‐1 involvement in pericyte loss induced by E scherichia coli in an in vitro model of blood brain barrier
Author(s) -
Salmeri Mario,
Motta Carla,
Anfuso Carmelina D.,
Amodeo Andrea,
Scalia Marina,
Toscano Maria A.,
Alberghina Mario,
Lupo Gabriella
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12121
Subject(s) - biology , pericyte , in vitro , escherichia coli , blood–brain barrier , receptor , vegf receptors , microbiology and biotechnology , cancer research , neuroscience , genetics , central nervous system , endothelial stem cell , gene
Summary The key aspect of neonatal meningitis is related to the ability of pathogens to invade the blood–brain barrier ( BBB ) and to penetrate the central nervous system. In the present study we show that, in an in vitro model of BBB , on the basis of co‐culturing primary bovine brain endothelial cells ( BBEC ) and primary bovine retinal pericytes ( BRPC ), E scherichia coli infection determines changes of transendothelial electrical resistance ( TEER ) and permeability ( P e) to sodium fluorescein. In the co‐culture model, within BBEC , bacteria are able to stimulate cytosolic and C a 2+ ‐independent phospholipase A 2 ( cPLA 2 and iPLA 2 ) enzyme activities. In supernatants of E . coli ‐stimulated co‐cultures, an increase in prostaglandins ( PGE 2 ) and VEGF production in comparison with untreated co‐cultures were found. Incubation with E . coli in presence of AACOCF 3 or BEL caused a decrease of PGE 2 and VEGF release. SEM and TEM images of BBEC and BRPC showed E . coli adhesion to BBEC and BRPC but only in BBEC the invasion occurs. VEGFR ‐1 but not VEGFR ‐2 blockade by the specific antibody reduced E . coli invasion in BBEC . In our model of BBB infection, a significant loss of BRPC was observed. Following VEGFR ‐1, but not VEGFR ‐2 blockade, or in presence of AACOCF 3 or BEL , elevated TEER values, reducedpermeability and BRPC loss were found. These data suggest that VEGFR ‐1 negatively regulates BRPC survival and its blockade protects the barrier integrity. PGs and VEGF could exert a biological effect on BBB , probably by BRPC coverage ablation, thus increasing BBB permeability. Our results show the role played by the BBEC as well as BRPC during a bacterial attack on BBB . A better understanding of the mechanisms by which E . coli enter the nervous system and how bacteria alter the communication between endothelial cells and pericytes may provide exciting new insight for clinical intervention.