Physical changes in temperature, pH, oxygen and mechanical stimuli derived from the environment, are important for regulating cell function and survival. Although the immune cells experience mechanical forces and pressures throughout their life cycle, little is known about how such mechanical processes regulate the immune cell function. In this study, we investigated the effects of cyclical stretch (CS)-induced mechanical stress, a condition in which immune cells experience in the heart, on murine macrophage RAW264.7 (RAW) cells.
CS stimulation of RAW cells evoked a marked release of nucleotides including ATP and ADP in a strength-dependent manner. The CS stimulation also initiated elevation of mRNAs for various pro-inflammatory factors, such as IL-1β, IL-6, COX-2 and monocyte chemoattractant protein-1 (MCP-1). In the presence of gadolinium (Gd³⁺), an inhibitor of stretch-activated channels, CS-induced ATP release and mRNA elevation of IL-1β, IL-6, COX-2 were attenuated. Under such condition, CS-induced MCP-1 mRNA expression was not affected by Gd³⁺. Treatment with apyrase, a nucleotide hydrolysis enzyme, to eliminate the effects of extracellular nucleotides did not affect the CS-induced MCP-1 mRNA expression.  
These results suggest that the CS activates macrophage function via Gd³⁺-sensitive stretch-activated channels. In contrast, additional mechanism other than CS-activated channels and autocrine stimulation by extracellular nucleotides may be involved in the CS-induced MCP-1 mRNA expression.