Colchicine inhibits macrophage motility and matrix degradation through microtubule disruption

Atherosclerosis is a chronic inflammatory process wherein macrophages play a central role in the evolution of arterial wall plaques in extracellular matrix. Colchicine, a drug used most commonly to treat gout, reduces immune cell motility and recruitment to inflamed joints by targeting microtubules. Colchicine also reduces cardiovascular events in patients with recent acute or chronic coronary disease, but the mechanisms are incompletely understood. To characterise the effect of low-dose colchicine on human and mouse macrophages, focusing on the microtubule cytoskeleton and macrophage function. Human monocytes were isolated from buffy coats and differentiated into macrophages (huMDM) in culture medium. Mouse bone marrow-derived macrophages (msBMM) were extracted from C57BL/6 mice and grown in culture medium to produce mature adherent macrophages. HuMDM treated with 10 nM colchicine showed marked morphological and functional changes associated with disruption of the microtubule cytoskeleton. Colchicine reduced the footprint area of huMDM by almost 50% and matrix degradation by 20%. In contrast, colchicine minimally affected the morphology of msBMM. However, it reduced the density of the microtubule cytoskeleton at the leading edge of msBMM with detectable disruption of microtubules, resulting in a significant decrease in motility. While msBMM appeared less susceptible to low-dose colchicine than huMDM, there was a measurable effect on their microtubules that resulted in reduced motility. Inhibition of huMDM matrix degradative capacity may contribute to colchicine's effect in reducing cardiovascular events. • Anti-inflammatory drug, colchicine, affected macrophages, crucial to atherosclerosis. • Human macrophages showed marked morphological and functional changes after colchicine. • These changes were associated with a loss of the microtubule cytoskeleton. • Colchicine lowered microtubule density in mouse macrophages, inhibiting motility. • Macrophage effects of colchicine may aid the stabilisation of atherosclerotic plaques.