S-nitrosylation of surfactant protein-D controls inflammatory function

Area of Science:

• Pulmonary immunology
• Innate immunity
• Post-translational modifications

Background:

• Pulmonary collectins, surfactant proteins A and D (SP-A, SP-D), regulate lung innate immunity.
• SP-D exhibits dual pro- and anti-inflammatory roles, but the underlying mechanisms are unclear.
• SP-D's unique multimeric structure, stabilized by N-terminal cysteines, differs from other collectins.

Purpose of the Study:

• To investigate the role of S-nitrosylation in regulating SP-D's structure and function.
• To elucidate the molecular mechanisms by which SP-D's inflammatory signaling is controlled.

Main Methods:

• In vitro and in vivo studies using a rodent acute lung injury model.
• Analysis of SP-D structure, including multimerization and cysteine status.
• Assessment of SP-D's effect on macrophage chemoattraction and p38 MAPK phosphorylation.

Main Results:

• SP-D cysteines are targets for S-nitrosylation by nitric oxide (NO).
• S-nitrosylation disrupts SP-D multimers, favoring trimeric forms (SNO-SP-D).
• SNO-SP-D, but not native SP-D, attracts macrophages and induces p38 MAPK phosphorylation via calreticulin/CD91.

Conclusions:

• Nitric oxide-mediated S-nitrosylation is a key regulator of SP-D's inflammatory signaling.
• Post-translational modification alters SP-D's quaternary structure, switching its immune function.
• This study provides novel insights into NO's role in innate immunity and protein regulation by S-nitrosylation.