Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Isoenzyme specific cyclooxygenase inhibitors: a whole cell assay system using the human erythroleukemic cell line Hel and the human monocytic cell line Mono Mac 6

Abstract

NSAIDs inhibit the conversion of arachidonic acid into Prostaglandin G(2) and Prostaglandin H 2 which is catalyzed by the enzyme cyclooxygenase (COX). Two genetically distinct isoforms have been discovered, COX 1 and COX 2. While COX 1 is thought to account for homeostatic amounts of eicosanoids, COX 2 is induced during inflammation leading to pathologic amounts of eicosanoids. Since NSAIDs inhibit both COX isoforms, antiinflammatory drug research has refocused to discovering COX 2 inhibitors that do not inhibit COX 1. For this purpose, we have developed a whole cell assay system using the human erythroleukemic cell line HEL as a source for COX 1 and the human monocytic cell line Mono Mac 6 as a source for COX 2. Mono Mac 6 cells express high amounts of COX 2 upon stimulation with lipopolysaccharide (LPS) in the absence of any detectable COX 1 protein. On the other hand, we find HEL cells to naturally express COX 1 protein, but not COX 2. Testing of a panel of NSAIDs as well as some COX 2 specific inhibitors showed that this assay system is suitable for identifying compounds that selectively inhibit either COX 1 or COX 2. This test system offers the advantage of assessing COX 1 and COX 2 inhibitors within the human species, within a similar test set up, and circumvents the need for tedious purification of either platelets or peripheral blood monocytes. (C) 1997 Elsevier Science Inc.