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Infection and Immunity, May 2000, p. 2854-2862, Vol. 68, No. 5
Department of
Medicine,1 Department of
Microbiology,2 The Center for Microbial
Pathogenesis,3 Department of
Anesthesiology,4 and Department of
Social and Preventative Medicine,5 State
University of New York at Buffalo, Buffalo, New York 14214
Received 3 September 1999/Returned for modification 10 January
2000/Accepted 27 January 2000
Enteric gram-negative bacilli cause a severe, often
life-threatening pneumonia. An improved understanding of the
pathogenesis of this infection may lead to improved treatment. Nearly
all of the responsible gram-negative bacilli possess capsular
polysaccharides and/or an O-specific antigen as part of their
lipopolysaccharide (LPS). We hypothesized that these surface
polysaccharides may modulate the pulmonary host response. To
investigate this, a rat pneumonitis model was used, and pulmonary
neutrophil influx, a critical aspect of host defense, was measured. To
assess for the effect of the capsule and O-specific antigen on this
host response, three proven, isogenic derivatives that are deficient in
capsular polysaccharide alone (CP9.137), the O-specific antigen moiety of the LPS alone (CP921), and both the capsular polysaccharide and
O-specific antigen (CP923), as well as their wild-type parent (CP9),
were used as challenge strains at various intratracheal challenge
inocula (CI). Total lung myeloperoxidase (MPO), a surrogate marker for
neutrophils, was measured for 15 h post-bacterial challenge. To
determine the effect of capsule and the O-specific antigen on the
measured MPO levels, a mathematical model was developed and used to
describe the MPO levels as a function of time for each CI of each of
the four strains. The results from this analysis demonstrated that in
the absence of the K54 capsule, 80.7 times the CI is necessary to
achieve the same maximum MPO level relative to K54 positive strains
(P < 0.0001). In contrast, a diametric effect was
observed in the absence of the O-specific antigen, where 0.13 times the
CI was necessary to achieve the same maximum MPO level relative to
O4-positive strains (P = 0.0032). No interactive effect was observed between the capsule and the O-specific antigen. These findings demonstrate that these surface polysaccharides modulate
pulmonary neutrophil influx and suggest that the K54 capsular
polysaccharide is a proinflammatory mediator and that the O4-specific
antigen attenuates the proinflammatory response. If these speculations
are substantiated, an understanding of how the capsule and the
O-specific antigen modulate host response could have significant
therapeutic implications. The potential use of biologic modulators
directed against the host response, as well as approaches based on
inactivating bacterial components (e.g., surface polysaccharides)
in attempts to modify sepsis syndromes, could be developed.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Capsular Polysaccharide and O-Specific Antigen
Divergently Modulate Pulmonary Neutrophil Influx in an
Escherichia coli Model of Gram-Negative Pneumonitis in
Rats
*
Corresponding author. Mailing address: Department of
Medicine, Division of Infectious Diseases, 3435 Main St., Biomedical Research Building, Rm. 141, Buffalo, NY 14214. Phone: (716) 829-2674. Fax: (716) 829-3889. E-mail: trusso{at}acsu.buffalo.edu.
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