HΜGB1/sRAGE levels differ significantly between transudates and exudates.

Area of Science:

• Immunology
• Cell Biology
• Pulmonary Medicine

Background:

• High mobility group box 1 (HMGB1) is an alarmin crucial for immunity and homeostasis, interacting with the receptor for advanced glycation end products (RAGE).
• HMGB1 and its decoy receptor, soluble RAGE (sRAGE), are implicated in pulmonary diseases but underexplored in pleural effusions.
• Pleural effusions (PEs) represent fluid accumulation in the pleural space, with various underlying causes.

Purpose of the Study:

• To quantify HMGB1 and sRAGE levels in different types of pleural effusions: transudative, malignant, and parapneumonic.
• To investigate the influence of varying HMGB1 concentrations in PEs on MeT-5A cell behavior, including adhesion, migration, and spheroid formation.
• To explore potential age-related differences in HMGB1 and sRAGE levels within pleural effusion patients.

Main Methods:

• Measurement of HMGB1 and sRAGE protein levels in transudative, malignant, and parapneumonic pleural effusions.
• In vitro incubation of MeT-5A cells with pleural effusion samples characterized by low and high HMGB1 levels.
• Assessment of MeT-5A cell adhesion, migration, and spheroid formation in response to different HMGB1 concentrations and PE types.

Main Results:

• Transudative PEs showed lower HMGB1 and higher sRAGE compared to malignant and parapneumonic PEs.
• Patients over 65 years had significantly lower HMGB1 and higher sRAGE levels than younger patients.
• High HMGB1 levels generally increased cell adherence; effects on migration and spheroid formation were context-dependent, varying with PE type.

Conclusions:

• The HMGB1/sRAGE axis exhibits distinct levels and functional impacts across different pleural effusion types.
• HMGB1's role in MeT-5A cell behavior is significantly modulated by the specific clinical context of the pleural effusion.
• These findings highlight the context-dependent nature of HMGB1's involvement in pleural diseases.