title: Intracellular phospholipase A2 expression and location in human macrophages: influence of synthetic material surface chemistry.
abstract: Phospholipase A(2) (PLA(2)) enzymes participate in a potent inflammatory pathway through the liberation of arachidonic acid upon hydrolysis of membrane glycerophospholipids. The presence of implanted polycarbonate-urethane (PCNU) materials, used in several medical applications, has the ability to influence inflammatory responses of human macrophages that are recruited to a tissue-material interface; however, the specific inflammatory pathways that are activated upon macrophage attachment to PCNU are largely unknown. Previous studies suggested the participation of PLA(2) pathways in material degradation with the use of chemical inhibitors, such as aristolochic acid (ARIST), however not accurately defining the specific PLA(2) enzymes involved. The current study aimed to establish specific groups of PLA(2) involved in the macrophage foreign body response to PCNU. ARIST was assessed for specific effects on secretory PLA(2) (sPLA(2)) protein expression and non-specific effects on key proteins, beta-actin and monocyte-specific esterase, implicated in the macrophage attack on PCNU materials. Macrophage attachment to PCNU materials induced increased intracellular expression of cytosolic PLA(2) (cPLA(2)), but not sPLA(2), relative to tissue culture polystyrene (TCPS) as detected by immunoblot analysis, demonstrating an early and delayed stimulation during the time course of increased cPLA(2) protein expression. Laser scanning confocal microscopy images indicated a change in location of cPLA(2) in macrophages adherent to PCNU surfaces compared to TCPS. This study has illustrated changes in macrophage cPLA(2) expression in response to cell-attachment to PCNU surfaces, demonstrating that the macrophage foreign body response to biomaterials induces a potent inflammatory pathway, which may lead to tissue damage near the site of material implantation.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Donna Lee M
authors.initials: DL
authors.lastname: Dinnes
authors.forename: J Paul
authors.initials: JP
authors.lastname: Santerre
authors.forename: Rosalind S
authors.initials: RS
authors.lastname: Labow
mesh_terms: D034341:Aristolochic Acids / Q000494:pharmacology; D001672:Biocompatible Materials; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008422:Materials Testing; D015394:Molecular Structure; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D011140:Polyurethanes / Q000737:chemistry*; D013499:Surface Properties; D020298:U937 Cells
chemical_list: D034341:Aristolochic Acids; D001672:Biocompatible Materials; D011140:Polyurethanes; C000228:aristolochic acid I; D010741:Phospholipases A