The correlation between difference in foreign body reaction between implant locations and cytokine and MMP expression.
The foreign body reaction (FBR) differs between subcutaneously and supra-epicardially implanted materials. We hypothesize that this is a result of differences in cytokine, chemokine and matrix metalloproteinase (MMP) dynamics. Therefore we applied collagen disks subcutaneously and on the epicardium in mice and analyzed the FBR from day 1 to 21. Both the influx of leukocytes and implant degradation were higher in supra-epicardially implanted collagen than in subcutaneously implanted material. This correlated with a higher gene expression of pro-inflammatory cytokines such as IL-1 and IL-6, and a lower expression of the anti-inflammatory cytokine IL-10. Furthermore, the higher supra-epicardial expression of PMN attractants CXCL1/KC and CXCL2/MIP2 correlated with a higher and prolonged PMN influx. The gene expression levels of collagen degrading MMPs, i.e. MMP8, MMP13 and MMP14 were similar in subcutaneous and supra-epicardial disks. However, the activity of these enzymes was markedly higher supra-epicardially. In addition, the MMP9 expression was higher supra-epicardially, suggesting a role for this enzyme in the degradation process. In conclusion, a strong pro-inflammatory milieu is generated after supra-epicardial implantation that enables prolonged PMN presence and activation. This, together with the high supra-epicardial MMP9 level, could explain the observed difference in Col-I degradation between locations.
Luttikhuizen
Daniel T
DT
Department of Pathology and Laboratory Medicine, Medical Biology Section, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
van Amerongen
Machteld J
MJ
de Feijter
Pieter C
PC
Petersen
Arjen H
AH
Harmsen
Martin C
MC
van Luyn
Marja J A
MJ
D000818:Animals; D002417:Cattle; D018925:Chemokines / Q000235:genetics; D024042:Collagen Type I / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism; D005549:Foreign-Body Reaction / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D020007:Implants, Experimental; D007962:Leukocytes / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology; D010496:Pericardium / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*
D018925:Chemokines; D024042:Collagen Type I; D016207:Cytokines; D012333:RNA, Messenger; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse