title: THP-1 monocytes up-regulate intercellular adhesion molecule 1 in response to pneumolysin from Streptococcus pneumoniae.
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.
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, Jackson, 39216, USA,
authors.forename: Justin
authors.initials: J
authors.lastname: Thornton
authors.forename: Larry S
authors.initials: LS
authors.lastname: McDaniel
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000378:metabolism* / Q000472:pathogenicity; D013301:Streptolysins / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic; D015854:Up-Regulation; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D018799:Intercellular Adhesion Molecule-1