Cellular and extracellular phospholipase A2 activity in zymosan pleurisy in rat.
The pleural exudate from rats treated intrapleurally with zymosan contains phospholipase A2 (PLA2) activity which is Ca2(+)-independent and optimally active at a neutral pH. This PLA2 activity was found in approximately equal amounts in both the cellular and extracellular fractions of the exudate. The Ca2(+)-independency of the PLA2's in the pleural exudate distinguishes them from plasma PLA2's and this suggests that the source of the exudate PLA2's is not plasma. The appearance of PLA2 activity in zymosan-induced pleural exudate correlates temporally with increases in exudate volume and pleural cell number. In all cases, the maximum response was seen 24 hr after zymosan challenge. All parameters of pleurisy and PLA2 activity are similarly sensitive to the steroid dexamethasone which has been hypothesized to act, in part, through the synthesis of PLA2 inhibitory peptides. In its entirety, this information suggests that there is a relationship between pleural PLA2 activity and the appearance of pleural inflammation (exudate volume and cells) and that PLA2 may play an important role in the initiation and propagation of this inflammatory process in rats. Furthermore, the zymosan-induced pleurisy model may serve as a useful model for the identification of PLA2 inhibitors with antiinflammatory activity.
Morgan
D W
DW
Department of Allergy and Inflammation, Hoffmann-LaRoche, Inc., Nutley, NJ 07110.
Anderson
C
C
Meyers
K
K
Coffey
J
J
Moody
K
K
Welton
A
A
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010996:Pleural Effusion / Q000201:enzymology; D010998:Pleurisy / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D015054:Zymosan
D003907:Dexamethasone; D015054:Zymosan; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium