Acute exposure to apolipoprotein a1 inhibits macrophage chemotaxis in vitro and monocyte recruitment in vivo

A molecule called cholesterol is an important component of the membranes found in cells and is also used to make some hormones and other useful molecules. However, cholesterol can also contribute to the formation of plaques in arteries, which can lead to a disease called atherosclerosis, the cause of heart attacks. Particles called high density lipoproteins (HDL) carry cholesterol around the body in the bloodstream and are thought to have anti-inflammatory properties. A protein called apoA1 is a major component of HDL particles and, acting as part of a HDL particle or alone, it removes cholesterol from cells. Atherosclerotic plaques form when white blood cells collect in places where the arteries are inflamed. The membranes that surround the white blood cells contain receptors that are able to detect inflammatory signals called chemokines. These receptors eventually communicate with the machinery needed for cell movement. This machinery is concentrated in parts of the membrane known as lipid rafts. Iqbal, Barrett et al. investigated whether apoA1 can block the movement of mouse and human white blood cells towards the chemokines produced during inflammation. The experiments show that apoA1 treatment strongly inhibited the movement of white blood cells towards a range of chemokines in a culture dish. The apoA1 protein removes cholesterol from lipid rafts in the membrane of the white blood cell, which changes the properties of the membrane and decreases the activity of the machinery needed for cell movement. Further experiments in mice with inflammation of the peritoneum, the thin layer of tissue that lines the inside of the abdomen, produced similar findings. The next step following on from this work would be to investigate whether apoA1 treatment can reduce the accumulation of white blood cells in mice that act as models of other inflammatory diseases, such as arthritis and atherosclerosis.