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Adhesion protein GMP140 inhibits superoxide anion release by human neutrophils
C S Wong1, J R Gamble, M P Skinner
1Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Abstract:
The respiratory burst of blood neutrophils has a critical role in the destruction of microorganisms and tissue damage in inflammation. Neutrophils adhere in a dose-dependent fashion to granule membrane protein 140 (GMP140), a member of the LEC-CAM (lectin/epidermal growth factor/complement-binding domain cell adhesion molecule) family of adhesion proteins when it is immobilized onto plastic surfaces. Adherence to GMP140 was associated with less superoxide anion generation than adherence to other surfaces, an effect that is especially remarkable after activation of neutrophils with tumor necrosis factor alpha, an agent that on other surfaces promotes adhesion and spreading. However, on GMP140 the cells fail to spread and instead remain rounded and refractile. Neutrophils adhering to GMP140 were also deficient in superoxide anion generation to formylmethionylleucylphenylalanine. Furthermore, fluid-phase GMP140 also inhibited the superoxide generation by neutrophils stimulated by tumor necrosis factor alpha. The effect of GMP140 was reversible by washing and was inhibited by anti-GMP140 Fab antibody. GMP140 appears to be a natural antiinflammatory molecule that may prevent the inappropriate activation of neutrophils in the circulation.
Insights
Granule membrane protein 140 (GMP140) on neutrophil surfaces reduces superoxide generation, acting as a natural anti-inflammatory molecule. This finding suggests GMP140 may prevent inappropriate neutrophil activation in circulation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Neutrophils play a key role in inflammation and host defense through their respiratory burst.
- Neutrophil adhesion is mediated by cell adhesion molecules, including LEC-CAMs like GMP140.
- The respiratory burst, involving superoxide anion generation, is crucial for neutrophil functions.
Purpose of the Study:
- To investigate the effect of GMP140 on neutrophil adherence and respiratory burst.
- To determine if GMP140 modulates neutrophil activation by inflammatory stimuli.
- To explore the potential anti-inflammatory role of GMP140.
Main Methods:
- Immobilizing GMP140 onto plastic surfaces to study neutrophil adherence.
- Measuring superoxide anion generation by neutrophils adhering to GMP140 and other surfaces.
- Stimulating neutrophils with tumor necrosis factor alpha and formylmethionylleucylphenylalanine.
- Investigating the effect of fluid-phase GMP140 and anti-GMP140 Fab antibody.
Main Results:
- Neutrophil adherence to GMP140 was dose-dependent and associated with reduced superoxide anion generation.
- GMP140 inhibited neutrophil spreading and superoxide generation even after activation with tumor necrosis factor alpha.
- Neutrophils adhering to GMP140 showed deficient superoxide generation in response to formylmethionylleucylphenylalanine.
- Fluid-phase GMP140 also inhibited tumor necrosis factor alpha-stimulated superoxide generation.
- The inhibitory effect of GMP140 was reversible and blocked by anti-GMP140 Fab antibody.
Conclusions:
- GMP140 acts as a natural anti-inflammatory molecule by inhibiting neutrophil respiratory burst.
- GMP140 may prevent inappropriate neutrophil activation and subsequent tissue damage in inflammatory conditions.
- This study highlights a novel regulatory mechanism of neutrophil function by GMP140.