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Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
Toll-like receptor 2 (TLR2)-mediated cell activation induced by
commercial preparations of LPS was recently shown to arise from
impurities whose identities are not known. In this work, we determined
the molecules responsible for TLR2-mediated cell activation in LPS
derived from Escherichia coli K-12 strain LCD25. When
LCD25 LPS was phenol extracted, two proteins capable of TLR2-mediated
cell activation were purified and identified as E. coli
lipoproteins. We cloned, expressed, and purified these two
lipoproteins, Lip19 and Lip12. Lip19 or Lip12 activated TNF-
production from RAW264.7 and THP-1 cells in a TLR2-dependent manner.
However, neither Lip19 nor Lip12 activated HUVECs, which lack
endogenous TLR2. Additionally, I
B kinase 
and c-Jun
N-terminal kinase 1 activation in THP-1 cells induced by Lip19 or Lip12
was observed. TLR2 activation by Lip19 and Lip12 in HEK293 cells was
blocked by inhibitory anti-TLR2 mAbs. The unlipidated mutants,
Lip19-C19S and Lip12-C21S, in which the NH2-terminal
cysteine was substituted by serine, lost their ability to activate
TLR2-transfected HEK 293 cells. Taken together, these results
demonstrate that two lipoproteins constitute the major contaminants
responsible for TLR2-mediated cell activation in E. coli
LCD25 LPS.
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