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Nitric oxide synthase is expressed in human macrophages during foreign body inflammation
E Moilanen1, T Moilanen, R Knowles
1Wellcome Research Laboratories, Beckenham, United Kingdom.
Abstract:
Although nitric oxide (NO) is a well documented effector molecule in rodent macrophages, its significance in human mononuclear phagocytic cells has been controversial. The foreign body inflammatory reaction around loosened joint replacement implants leads to formation of an osteolytic granulomatous pseudo-synovial membrane rich in activated macrophages. We studied 13 specimens of interface membrane tissue collected from revision surgery of aseptically loosened hip and knee prostheses for the presence of inducible NO synthase (iNOS). The presence of iNOS was demonstrated immunohistochemically in 10 of these specimens. Within the tissue this enzyme was confined to macrophages and vascular endothelial cells. iNOS activity was demonstrated biochemically by measuring the calcium-independent generation of citrulline from L-arginine, and the presence of iNOS mRNA was demonstrated using reverse transcriptase polymerase chain reaction. NO synthesis in the interface tissue may be an important factor in the maintenance of the inflammatory and osteolytic processes.
Insights
This study found inducible nitric oxide synthase (iNOS) in human macrophages near loosened joint implants. This suggests nitric oxide (NO) plays a role in implant-associated inflammation and bone loss.
Area of Science:
- Immunology
- Biochemistry
- Orthopedic Surgery
Background:
- The role of nitric oxide (NO) in human macrophages is debated.
- Loosened joint replacements trigger inflammation and bone loss due to macrophage activation.
Purpose of the Study:
- Investigate the presence and significance of inducible NO synthase (iNOS) in human macrophages within interface membranes of loosened joint prostheses.
Main Methods:
- Immunohistochemistry to detect iNOS protein in tissue specimens.
- Biochemical assays to measure iNOS activity via citrulline generation.
- Reverse transcriptase polymerase chain reaction (RT-PCR) to detect iNOS mRNA.
Main Results:
- iNOS was detected in 10 out of 13 interface membrane specimens.
- iNOS was localized to macrophages and vascular endothelial cells.
- Biochemical and molecular evidence confirmed iNOS activity and expression.
Conclusions:
- Inducible NO synthase (iNOS) is present in human macrophages associated with loosened joint implants.
- NO synthesis may contribute to the inflammatory and osteolytic processes around these implants.