TY - JOUR
T1 - Escherichia coli Braun Lipoprotein (BLP) exhibits endotoxemia - Like pathology in Swiss albino mice
AU - Lakshmikanth, Chikkamenahalli Lakshminarayana
AU - Jacob, Shancy Petsel
AU - Kudva, Avinash Kundadka
AU - Latchoumycandane, Calivarathan
AU - Yashaswini, Puttaraju Srikanta Murthy
AU - Sumanth, Mosale Seetharam
AU - Goncalves-De-Albuquerque, Cassiano F.
AU - Silva, Adriana R.
AU - Singh, Sridevi Annapurna
AU - Castro-Faria-Neto, Hugo C.
AU - Prabhu, Sandeep Kumble
AU - McIntyre, Thomas M.
AU - Marathe, Gopal Kedihithlu
N1 - Publisher Copyright:
© The Author(s) 2016.
PY - 2016/10/4
Y1 - 2016/10/4
N2 - The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides also promote inflammation leading to sepsis. We found, intraperitoneal administration of live or heat inactivated E. coli JE5505 lacking the abundant outer membrane protein, Braun lipoprotein (BLP), was less toxic than E. coli DH5α possessing BLP in Swiss albino mice. Injection of BLP free of LPS purified from E. coli DH5α induced massive infiltration of leukocytes in lungs and liver. BLP activated human polymorphonuclear cells (PMNs) ex vivo to adhere to denatured collagen in serum and polymyxin B independent fashion, a property distinct from LPS. Both LPS and BLP stimulated the synthesis of platelet activating factor (PAF), a potent lipid mediator, in human PMNs. In mouse macrophage cell line, RAW264.7, while both BLP and LPS similarly upregulated TNF-α and IL-1β mRNA; BLP was more potent in inducing cyclooxygenase-2 (COX-2) mRNA and protein expression. Peritoneal macrophages from TLR2 -/- mice significantly reduced the production of TNF-α in response to BLP in contrast to macrophages from wild type mice. We conclude, BLP acting through TLR2, is a potent inducer of inflammation with a response profile both common and distinct from LPS. Hence, BLP mediated pathway may also be considered as an effective target against sepsis.
AB - The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides also promote inflammation leading to sepsis. We found, intraperitoneal administration of live or heat inactivated E. coli JE5505 lacking the abundant outer membrane protein, Braun lipoprotein (BLP), was less toxic than E. coli DH5α possessing BLP in Swiss albino mice. Injection of BLP free of LPS purified from E. coli DH5α induced massive infiltration of leukocytes in lungs and liver. BLP activated human polymorphonuclear cells (PMNs) ex vivo to adhere to denatured collagen in serum and polymyxin B independent fashion, a property distinct from LPS. Both LPS and BLP stimulated the synthesis of platelet activating factor (PAF), a potent lipid mediator, in human PMNs. In mouse macrophage cell line, RAW264.7, while both BLP and LPS similarly upregulated TNF-α and IL-1β mRNA; BLP was more potent in inducing cyclooxygenase-2 (COX-2) mRNA and protein expression. Peritoneal macrophages from TLR2 -/- mice significantly reduced the production of TNF-α in response to BLP in contrast to macrophages from wild type mice. We conclude, BLP acting through TLR2, is a potent inducer of inflammation with a response profile both common and distinct from LPS. Hence, BLP mediated pathway may also be considered as an effective target against sepsis.
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U2 - 10.1038/srep34666
DO - 10.1038/srep34666
M3 - Article
C2 - 27698491
AN - SCOPUS:84990242033
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 34666
ER -