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Redox regulation of beta2-integrin CD11b/CD18 activation
E Blouin1, L Halbwachs-Mecarelli, P Rieu
1INSERM U507, Department of Nephrology, Necker Hospital, Paris, France.
European Journal of Immunology
|November 11, 1999
Summary
Oxidation mechanisms, specifically hydrogen peroxide (H2O2), are crucial for activating beta2-integrin CD11b/CD18 in neutrophils. This oxidative process, involving tyrosine kinases, regulates neutrophil adhesion and migration.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- The beta2-integrin CD11b/CD18 plays a key role in neutrophil functions.
- Signaling pathways regulating integrin activation are not fully understood.
Purpose of the Study:
- To investigate the role of oxido-reduction mechanisms in regulating beta2-integrin CD11b/CD18 activation.
- To elucidate the signaling pathways involved in integrin activation.
Main Methods:
- Studied the effects of hydrogen peroxide (H2O2) on neutrophil adhesion and integrin activation.
- Utilized tyrosine kinase inhibitors, phenylarsine oxide (PAO), diphenylene iodonium (DPI), and free radical scavengers.
- Examined neutrophils from patients with chronic granulomatous disease.
Main Results:
- Exogenous H2O2 induced CD11b/CD18-dependent neutrophil adhesion and a specific integrin activation neoepitope.
- H2O2-triggered activation was inhibited by tyrosine kinase inhibitors and PAO.
- Physiological agonists like TNF-alpha also triggered activation, inhibited by DPI, scavengers, tyrosine kinase inhibitors, and PAO, but not by direct integrin activation (KIM 185 mAb).
- The identified pathway is independent of NADPH oxidase.
Conclusions:
- Oxidative S-thiolation is a critical step in the tyrosine kinase-dependent signaling pathway for beta2-integrin activation.
- H2O2 directly mediates this oxidative reaction, bypassing initial receptor pathways to promote adhesion.
- These findings provide new insights into the regulation of integrin activation for neutrophil migration to inflamed tissues.