In vivo administration of tolmetin in hyaluronic acid modulates protease levels in postsurgical macrophage-conditioned media.
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 suppressed 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.
Rodgers
K E
KE
Livingston Reproductive Biology Laboratory, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles 90033.
Abe
H
H
Campeau
J D
JD
Ellefson
D D
DD
Girgis
W
W
diZerega
G S
GS
D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis; D010450:Endopeptidases / Q000096:biosynthesis*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006820:Hyaluronic Acid; D007274:Injections, Intraperitoneal; D007813:Laparotomy; D008264:Macrophages / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000096:biosynthesis; D010529:Peritoneal Cavity / Q000166:cytology; D010960:Plasminogen Activators / Q000096:biosynthesis; D015849:Plasminogen Inactivators / Q000096:biosynthesis; D011184:Postoperative Period; D011817:Rabbits; D014046:Tolmetin / Q000494:pharmacology*; D014599:Uterus / Q000601:surgery
D017077:Culture Media, Conditioned; D015849:Plasminogen Inactivators; D006820:Hyaluronic Acid; D004247:DNA; D014046:Tolmetin; D010450:Endopeptidases; D010960:Plasminogen Activators; D010196:Pancreatic Elastase; D017364:Collagenases