Model systems to assess the destructive potential of human neutrophils andmonocyte-derived macrophages during the acute and chronic phases of inflammation

Isolated cell systems of human neutrophils (PMNs) and monocyte-derived macr ophages (MDMs) were used to compare the destructive potential of these cell s during the acute and chronic phases of inflammation, respectively. The co ntrast in the damage to poly(urethane)s (PUs) was monitored by measuring ra diolabel release elicited from a C-14-polyester-urea-urethane (PEUU) during incubation with both cell types. Human PMN were seeded onto polymer-coated glass slips and both radiolabel release as well as serine protease activit y [assayed with N-benzyloxycarbonyl lysine thiobenzyl ester (BLT)] were mea sured 18 h later. Human monocytes were cultured on polystyrene tissue cultu re plates for 14 days, trypsinized, and seeded onto the polymer-coated glas s sips; then, radiolabel release and esterase activity [assayed with p-nitr ophenylbutyrate (PNB)] were measured after 18 h. Coverslips with MDM were a lso incubated for an additional 2 weeks. At 18 h postincubation with the PE UU, MDM elicited 25 times more radiolabel release per 10(6) cells than PMN at 18 h and continued to increase more than sevenfold over the 18-h value d uring the subsequent 14-day period. The BLT activity in PMN did not increas e significantly during the 18-h incubation period, whereas the PNB activity in MDM increased more than fourfold. The MDM, but not the PMN elicited rad iolabel release, was inhibited by the protein synthesis inhibitor cyclohexi mide, as was the increase in PNB activity. The data provide evidence for a hydrolytic role for MDM and, to a lesser extent PMN, in the biodegradation of implanted materials. The full implication of the release of polymer-deri ved chemical agents from this hydrolytic cleavage of the implanted biomater ials, on the propagation of the inflammatory response, remains to be elucid ated. (C) 2000 John Wiley & Sons, Inc.