Labow R S, Meek E, Santerre J P
Cardiovascular Devices Division, University of Ottawa Heart Institute, ON, Canada.
J Cell Physiol. 2001 Jan;186(1):95-103. doi: 10.1002/1097-4652(200101)186:1<95::AID-JCP1008>3.0.CO;2-0.
During the acute inflammatory response to implanted medical devices, human neutrophils (PMN) release oxidative and hydrolytic activities which may ultimately contribute to the degradation of the biomaterial. In this study, the biological activities secreted by live PMNs which may contribute to biodegradation were investigated using a 14C label in the monomer unit of a poly(ester-urea-urethane) (PEUU) substrate. By using specific inhibitors, it was possible to propose a mechanism for PMN-mediated biodegradation. PMN, labeled with 3H-arachidonic acid, released significantly more 3H when adherent to PEUU than when adherent to tissue culture grade polystyrene (P<0.05). The phospholipase A2 (PLA2) inhibitors, aristolochic acid (ARIST) and quinacrine (QUIN), decreased the release of 3H and inhibited PEUU biodegradation (>50%, P<0.05). ARIST had no effect on cell viability, whereas QUIN significantly decreased it. The serine protease inhibitor, phenylmethylsulfonylfluoride inhibited biodegradation, but did not decrease cell survival. There is evidence to suggest that activation via the PLA2 pathway caused the release of hydrolytic activities which were able to elicit 14C release from PEUU. The role of oxidative compounds which were released via activation by phorbol myristate acetate (PMA), was not apparent, since PMA inhibited biodegradation and cell survival (>40%, P<0.05). This study has shown that it is possible to find out the differences in PMN activation through the PLA2 pathway when exposed to different material surfaces, making this a model system worthy of further investigation.
