Oxidized N-3 fatty acids inhibit phagocyte adhesion to peritoneal pet implants

Sanjeev M Sethi, L. P. Tang, J. W. Eaton

Research output: Contribution to journalArticle

Abstract

Biomaterials mediate a variety of adverse reactions including inflammation, fibrosis and coagulation. Micromolar concentrations of polyunsaturated n-3 fatty acids, docosahexanoic and eicosapentanoic acid (EPA), present in large amounts in oils of marine fish, will decrease the binding of phagocytes to endothelial surfaces. Only oxidized n-3 PUFA are effective and these block not only the induction of VCAM-1 and ELAM-1 (mRNA and product) but also the activation/nuclear translocation of NFκB (Sethi et al., J. Lab. Clin. Med. 128:27, 1996). To determine whether oxidized EPA may decrease biomaterial associated inflammation by preventing phagocyte adhesion to biomaterial surfaces, polyester terephthalate (PET) disks were implanted subcutaneously, adjacent to the peritoneum of Swiss webster mice (male, 20 grams). The mice were injected intraperitoneally with either 0.1 ml oxidized EPA (3.3mM) or saline, 12 hours prior to and 1 hour after implantation. PET disks were explantated at 24 hrs and adherent phagocytes to the PET disks were quantified by enzymatic assay-myeloperoxidase for neutrophils and non specific esterase for monocytes. The number of monocytes and neutrophils adherent to the PET disks was reduced by 75% and 10%, respectively, in mice pretreated with oxidized EPA when compared to mice pretreated with saline only. Examination of peritoneal and subcutaneous tissue in hematoxylin and eosin stained sections showed a layer of mononuclear cells adjacent to the implant in mice pretreated with saline, while there was a marked reduction in the number of mononuclear cells in mice pretreated with oxidized EPA. More importantly, in mice pretreated with oxidized EPA there were many mononuclear cells within dilated blood vessels, indicating that while the mononuclear cells were attracted to the implant they were unable to cross the endothelial lining of blood vessels. These studies indicate that oxidized n-3 fatty acids may prevent ingress of monocytes to biomaterial surfaces and may decrease biomaterial associated chronic inflammation and fibrosis.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

Fingerprint

prostheses
Eicosapentaenoic Acid
phagocytes
Pets
Omega-3 Fatty Acids
Phagocytes
pets
Biocompatible Materials
adhesion
biocompatible materials
Polyesters
Adhesion
fatty acids
polyesters
mice
acids
monocytes
Monocytes
Blood vessels
inflammation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Oxidized N-3 fatty acids inhibit phagocyte adhesion to peritoneal pet implants. / Sethi, Sanjeev M; Tang, L. P.; Eaton, J. W.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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abstract = "Biomaterials mediate a variety of adverse reactions including inflammation, fibrosis and coagulation. Micromolar concentrations of polyunsaturated n-3 fatty acids, docosahexanoic and eicosapentanoic acid (EPA), present in large amounts in oils of marine fish, will decrease the binding of phagocytes to endothelial surfaces. Only oxidized n-3 PUFA are effective and these block not only the induction of VCAM-1 and ELAM-1 (mRNA and product) but also the activation/nuclear translocation of NFκB (Sethi et al., J. Lab. Clin. Med. 128:27, 1996). To determine whether oxidized EPA may decrease biomaterial associated inflammation by preventing phagocyte adhesion to biomaterial surfaces, polyester terephthalate (PET) disks were implanted subcutaneously, adjacent to the peritoneum of Swiss webster mice (male, 20 grams). The mice were injected intraperitoneally with either 0.1 ml oxidized EPA (3.3mM) or saline, 12 hours prior to and 1 hour after implantation. PET disks were explantated at 24 hrs and adherent phagocytes to the PET disks were quantified by enzymatic assay-myeloperoxidase for neutrophils and non specific esterase for monocytes. The number of monocytes and neutrophils adherent to the PET disks was reduced by 75{\%} and 10{\%}, respectively, in mice pretreated with oxidized EPA when compared to mice pretreated with saline only. Examination of peritoneal and subcutaneous tissue in hematoxylin and eosin stained sections showed a layer of mononuclear cells adjacent to the implant in mice pretreated with saline, while there was a marked reduction in the number of mononuclear cells in mice pretreated with oxidized EPA. More importantly, in mice pretreated with oxidized EPA there were many mononuclear cells within dilated blood vessels, indicating that while the mononuclear cells were attracted to the implant they were unable to cross the endothelial lining of blood vessels. These studies indicate that oxidized n-3 fatty acids may prevent ingress of monocytes to biomaterial surfaces and may decrease biomaterial associated chronic inflammation and fibrosis.",
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