Potentiated macrophage activation by acid sensing under low adiponectin levels

•Acid stimulation induced increasing intra-cellular Ca2+ concentration in macrophages.•Ca2+ mobilization of macrophages by acid stimulation attributed to the combination of acid-sensing ion channels (ASICs) and Na+/Ca2+ exchangers (NCXs).•Low adiponectin levels reduced threshold of the acid sensing mechanism of macrophages. Adiponectin can protect against inflammation; one of the mechanisms involves direct, inhibition of macrophages (MΦ). We postulated that adiponectin anti-sense transgenic (AsTg) mice raised in our laboratory are prone to inflammation because of systemic low adiponectin levels. The writhing response to acetic acid was utilized as an in vivo inflammatory model, and using Ca2+, response to the acid was exploited in vitro to evaluate the function of resident peritoneal MΦ. The in vivo response to the acid was increased and the Ca2+ response of MΦ was enhanced in AsTg mice, compared with those in wild type (WT) mice. In parallel with these enhanced responses, MΦ from AsTg mice augmented TNF-α and IL-6 mRNA expression. We further analyzed the enhancement in activity of MΦ from AsTg mice by acid sensing using specific inhibitors, amiloride for acid-sensing ion channels (ASICs) and KB-R7943 for Na+/Ca2+ exchangers (NCXs). Our results indicated that in AsTg mice, the Ca2+ response to the acid was facilitated in MΦ by a low threshold of ASIC1 and NCX1 molecules and the activity of these channel was possibly regulated by adiponectin.