In vivo administration of tolmetin in hyaluronic acid modulates protease levels in postsurgical macrophage-conditioned media

Kathleen E. Rodgers, Hiromasa Abe, Joseph D. Campeau, Dolph D. Ellefson, Wefki Girgis, Gere S. Dizerega

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Tolmetin sodium in a hyaluronic acid carrier (tolmetin-HA) was previously shown to reduce adhesion formation and alter the kinetics and levels of cellular influx into the peritoneal cavity after surgery. In this study, the effect of tolmetin-HA on the level of protease activity in macrophage-conditioned media was determined. The level of collagenase activity in macrophage-conditioned media was supressed at 12 and 24 h after administration of tolmetin-HA. Alternatively, the peak level of elastase activity measured in macrophage-conditioned media was unchanged after tolmetin-HA treatment, but the kinetics of expression of maximal protease activity was delayed from 12 h in the control surgical rabbits to 24 h in tolmetin-HA-treated rabbits. Elevated plasminogen activator activity was detected in acid-treated conditioned media from the tolmetin-HA-treated rabbits when compared to control levels. However, no alteration in the level of plasminogen activator inhibitor activity was present in conditioned media of macrophages harvested from tolmetin-HA-treated rabbits compared to controls. These data suggest that tolmetin-HA treatment altered the levels of neutral protease activity secreted by postsurgical macrophages and may therefore elevate the fibrinolytic potential of the peritoneal cavity after surgery.

Original languageEnglish (US)
Pages (from-to)285-296
Number of pages12
JournalJournal of Investigative Surgery
Volume5
Issue number4
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • Adhesions
  • Macrophage
  • NSAID
  • Protease
  • Tolmetin

ASJC Scopus subject areas

  • Surgery

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