1. THP-1 monocytes up-regulate intercellular adhesion molecule 1 in response to pneumolysin from Streptococcus pneumoniae.
- Author
-
Thornton J and McDaniel LS
- Subjects
- Bacterial Proteins metabolism, Bacterial Proteins pharmacology, Cells, Cultured, Humans, Intercellular Adhesion Molecule-1 genetics, Monocytes drug effects, RNA, Messenger analysis, RNA, Messenger metabolism, Recombinant Proteins metabolism, Recombinant Proteins pharmacology, Streptococcus pneumoniae pathogenicity, Streptolysins pharmacology, Transcription, Genetic, Up-Regulation, Virulence, Intercellular Adhesion Molecule-1 metabolism, Monocytes metabolism, Streptococcus pneumoniae metabolism, Streptolysins metabolism
- Abstract
Pneumolysin (PLY) is a major virulence factor of Streptococcus pneumoniae that elicits a variety of proinflammatory responses from cells of the host immune system. Intercellular adhesion molecule 1 (ICAM-1) is a cell adhesion molecule involved in leukocyte trafficking toward inflammatory stimuli in extravascular sites. In this study, we evaluated the effect of PLY on expression of ICAM-1 in THP-1 monocytic cells exposed to S. pneumoniae. Exposure of cells to PLY-expressing S. pneumoniae strain WU2 for 6 h led to significantly higher levels of ICAM-1 message than those in cells exposed to either medium alone or DeltaPLY1, a PLY-negative isogenic mutant of WU2. Cells exposed to purified recombinant PLY also showed a dose-dependent increase in ICAM-1 mRNA compared to cells exposed to medium alone. Exposure to recombinant PLY containing a single amino acid substitution (Trp433-->Phe) that decreases cytolytic activity did not increase ICAM-1 mRNA to levels seen with wild-type PLY. In addition, THP-1 cells exposed to wild-type strain WU2 or D39 had increased ICAM-1 on their surface compared to cells exposed to medium alone or their PLY-negative isogenic mutants DeltaPLY1 and DeltaPLY2, respectively. These data indicate that PLY induces transcription and production of a cell adhesion molecule involved in the inflammatory response that may play a role in pneumococcal infection.
- Published
- 2005
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