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

Isolated cell systems of human neutrophils (PMNs) and monocyte-derived macrophages (MDMs) were used to compare the destructive potential of these cells during the acute and chronic phases of inflammation, respectively. The contrast in the damage to poly(urethane)s (PUs) was monitored by measuring radiolabel release elicited from a (14)C-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 activity [assayed with N-benzyloxycarbonyl lysine thiobenzyl ester (BLT)] were measured 18 h later. Human monocytes were cultured on polystyrene tissue culture plates for 14 days, trypsinized, and seeded onto the polymer-coated glass slips; then, radiolabel release and esterase activity [assayed with p-nitrophenylbutyrate (PNB)] were measured after 18 h. Coverslips with MDM were also incubated for an additional 2 weeks. At 18 h postincubation with the PEUU, 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 during the subsequent 14-day period. The BLT activity in PMN did not increase significantly during the 18-h incubation period, whereas the PNB activity in MDM increased more than fourfold. The MDM, but not the PMN elicited radiolabel release, was inhibited by the protein synthesis inhibitor cycloheximide, 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-derived chemical agents from this hydrolytic cleavage of the implanted biomaterials, on the propagation of the inflammatory response, remains to be elucidated.