THE MECHANISM OF CARRAGEENAN INDUCED INFLAMMATION IN RAT

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Cells isolated from the pleural cavity of rat consisted mainly of macrophages, mast cells, eosinophils, lymphocytes and mesothelial cells. Isolated pleural cells labeled with [14C]-arachidonic acid released substantial amounts of radiolabel upon exposure to pharmacologically relevant concentration of carrangeenan (l-100 ug/ml). The time course of release was also compatible with the in vivo inflammatory action of carrageenan. An inhibitor of phospholipase A2 (i.e., p-bromophenacyl bromide) but not of arachidonate cyclooxygenase (i.e., indomethacin) inhibited the release in a dose-dependent manner. Analysis (by HPLC and radioimmunoassay) of the released products indicated that more than 90% of the radiolabel was arachidonic acid. Carrageenan also caused significant release of lactate dehydrogenase (LDH) from pleural cells. Release of LDH generally paralleled release of radiolabel although release of radiolabel preceded that of LDH. That the two events did not bear a cause-effect relationship, however, was demonstrated by the failure of p-bromophenacyl bromide to block release of LDH.