Potentiated macrophage activation by acid sensing under low adiponectin levels

Area of Science:

• Immunology
• Molecular Biology
• Physiology

Background:

• Adiponectin is known to possess anti-inflammatory properties.
• A key mechanism involves the direct inhibition of macrophages (MΦ).
• Adiponectin anti-sense transgenic (AsTg) mice exhibit low systemic adiponectin levels, suggesting potential inflammation susceptibility.

Purpose of the Study:

• To investigate the link between low adiponectin levels and inflammation in AsTg mice.
• To evaluate the functional changes in macrophages from AsTg mice.
• To explore the role of acid-sensing ion channels (ASICs) and Na+/Ca2+ exchangers (NCXs) in adiponectin-mediated macrophage responses.

Main Methods:

• Utilized an acetic acid-induced writhing response as an in vivo inflammatory model.
• Assessed in vitro Ca2+ responses of peritoneal macrophages to acid.
• Measured TNF-α and IL-6 mRNA expression in macrophages.
• Employed specific inhibitors (amiloride for ASICs, KB-R7943 for NCXs) to analyze acid-sensing mechanisms.

Main Results:

• AsTg mice displayed an increased writhing response to acetic acid compared to wild-type (WT) mice.
• Macrophages from AsTg mice exhibited enhanced Ca2+ responses to acid.
• Elevated TNF-α and IL-6 mRNA expression was observed in macrophages from AsTg mice.
• Acid-induced Ca2+ responses in AsTg mouse macrophages were facilitated by a lower threshold of ASIC1 and NCX1.

Conclusions:

• Systemic reduction of adiponectin in AsTg mice leads to heightened inflammation and enhanced macrophage reactivity.
• Adiponectin may regulate macrophage activity, particularly their acid-sensing capabilities via ASIC1 and NCX1.
• These findings highlight adiponectin's crucial role in modulating inflammatory responses at the macrophage level.