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Infection and Immunity, May 1999, p. 2371-2376, Vol. 67, No. 5
University of Colorado Health Sciences
Center, Denver, Colorado 80262
Received 3 December 1998/Returned for modification 21 January
1999/Accepted 24 February 1999
Pseudomonas aeruginosa is a persistent pathogen in the
airways of patients with cystic fibrosis or bronchiectasis from
other causes and appears to have evolved strategies to survive the
inflammatory response of the host. We hypothesized that the secreted
hemolytic phospholipase C (PLC) of P. aeruginosa (PlcHR)
would decrease neutrophil respiratory burst activity. We
found that while intact wild-type P. aeruginosa cells
stimulated moderate respiratory burst activity from human neutrophils,
an isogenic mutant pseudomonas (
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Pseudomonas aeruginosa Hemolytic
Phospholipase C Suppresses Neutrophil Respiratory Burst
Activity
HR strain) containing a targeted
deletion of the plcHR operon induced a much more robust
oxidative burst from neutrophils. In contrast, a second
pseudomonas mutant (
N) containing a disruption in the gene encoding
the nonhemolytic PLC (PlcN) was not different from the
wild type in stimulating neutrophil O2·
production. Readdition of purified PlcHR to the
HR strain suppressed neutrophil O2·
production to levels stimulated by wild-type bacteria.
Interestingly, purified PlcHR decreased phorbol myristate
acetate (PMA)- but not formyl methionyl-leucyl-proline
(fMLP)-induced respiratory burst activity, suggesting interference
by PlcHR with a protein kinase C (PKC)-specific signaling pathway.
Accordingly, the PKC inhibitor bisindolylmaleimide inhibited the
oxidative burst induced by either PMA or intact pseudomonas,
but not by fMLP, whereas the p38 kinase inhibitor SB-203580
fully inhibited the respiratory burst induced by fMLP or
the PlcHR-replete wild-type bacteria, but not PMA or the
PlcHR-deficient
HR bacterial mutant. We conclude that
expression of PlcHR by P. aeruginosa suppresses
bacterium-induced neutrophil respiratory burst by interfering
with a PKC-dependent, non-p38 kinase-dependent pathway.
*
Corresponding author. Present address: Dallas VAMC and
UT Southwestern, Pulmonary and Critical Care (111F), 4500 S. Lancaster Rd., Dallas, TX 75216. Phone: (214) 857-1475. Fax: (214) 857-0340. E-mail: lterada{at}aol.com.
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