HEMIN MODIFIED LPS EFFECTS ON PMN FUNCTION

Project: Research project

Project Details

Description

Lipopolysaccharides (LPS) are among the most potent cell agonists known:
LPS can act at picomolar concentrations to trigger the release of toxic
oxygen radicals and cytokines from inflammatory cells. The LPS from the
opportunistic oral pathogen, Porphyromonas gingivalis (Pg), possess little
proinflammatory activity according to some reports, while other reports
contradict these findings. Our published studies indicate that the level
of hemin in the growth media can have a profound effect on the LPS of Pg.
Hemin replete growth conditions (H+)result in specific morphologic and
antigenic modifications of Pg LPS; moreover, hemin-replete LPS from Pg
(H+LPS) is more biologically active when compared with LPS from hemin-
depleted Pg (H-LPS). This activity includes increased PMN priming and
increased binding to LPS-binding protein (LBP). Interestingly, H+Pg whole
cells are more readily phagocytosed than H-Pg, but are not killed by PMN
intracellularly, suggesting that fundamental changes to the outer membrane
of Pg are induced under H+ conditions.

We propose to test the following hypotheses:

Hypothesis 1: Under hemin-replete growth conditions, Pg produces an LPS
moiety (H+LPS) that is different structurally from that produced under
hemin-depleted growth conditions (H-LPS)

Hypothesis 2: The increased biological activity of H+LPS is dependent on
its binding affinity for LPS-binding protein (LBP) and its effects on CD14
expression on PMN>

We propose the following specific aims to test these hypotheses:

Specific aim 1: To characterize H+LPS and H-LPS from Pg structurally and
biochemically.
Specific aim 2: To determine the roles for LBP affinity and/or increased
PMN CD14 expression in activation of PMNs by H+LPS from Pg.

It is anticipated that the additional data and publications generated in
these studies will help the principal investigator in preparing a
successful F.I.R.S.T. award application.
StatusFinished
Effective start/end date3/15/973/14/99

ASJC

  • Medicine(all)
  • Dentistry(all)