Secretoglobin 1A1 and 1A1A differentially regulate neutrophil reactive oxygen species production, phagocytosis and extracellular trap formation.
Authors: Côté Olivier, Clark Mary Ellen, Viel Laurent, Labbé Geneviève, Seah Stephen Y K, Khan Meraj A, Douda David N, Palaniyar Nades, Bienzle Dorothee
Journal: PloS one
Summary
# Editorial Summary: Secretoglobin Isoforms and Neutrophil Function in Equine Airway Disease Secretoglobin 1A1 (SCGB 1A1) is a small anti-inflammatory protein abundant in airway secretions that is notably depleted in horses with recurrent airway obstruction (RAO); however, the precise mechanisms by which this protein regulates neutrophil behaviour have remained unclear until now. Researchers produced two distinct recombinant isoforms—SCGB 1A1 and SCGB 1A1A—that naturally occur in equids and examined their effects on neutrophil oxidative burst, phagocytosis, chemotaxis and neutrophil extracellular trap (NET) formation using ex vivo equine models. The two isoforms demonstrated both overlapping and divergent functions: whilst SCGB 1A1A enhanced reactive oxygen species production and phagocytosis, both proteins significantly suppressed neutrophil chemotaxis and NET formation in a concentration-dependent manner, with SCGB 1A1A showing greater inhibition of migration. Clinical findings revealed that bronchial tissue expression and bronchoalveolar lavage fluid concentrations of these secretoglobins were reduced in RAO-affected horses, and notably, NETs were detected in lavage samples only from horses experiencing acute RAO exacerbation, not during remission or in healthy controls. These findings suggest that altered ratios of SCGB isoforms in airways may directly contribute to excessive neutrophilic inflammation characteristic of RAO, offering potential therapeutic targets for modulating aberrant neutrophil activation in equine and other neutrophil-driven respiratory conditions.
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Practical Takeaways
- •The two distinct SCGB proteins have different immunomodulatory effects on neutrophils; reduced SCGB expression in RAO horses may contribute to excessive neutrophilic inflammation and NET formation
- •Understanding SCGB function may lead to targeted therapeutic interventions to restore anti-inflammatory balance in equine RAO
- •NET presence in BAL fluid during RAO exacerbation could serve as a biomarker to identify active disease and assess treatment response
Key Findings
- •SCGB 1A1A but not SCGB 1A1 increases neutrophil oxidative burst and phagocytosis
- •Both SCGB 1A1 and 1A1A significantly reduce neutrophil chemotaxis in time- and concentration-dependent manner
- •NET formation was significantly reduced by both SCGB proteins
- •SCGB mRNA and protein expression is lower in horses with RAO compared to controls, and NETs are present in BAL fluid during RAO exacerbation but not remission