CCL4 and alpha 1-antitrypsin deficiency: In addition to IL-8 and GM-CSF, we detected significant increases in secretion levels of IL-1Ra, MIP-1a and MIP-1b from AATD macrophages compared to normal macrophages in response to 24 h of exposure to cigarette smoke induced EVs, which is in line with cytokine profiles of patients with cigarette smoke-induced COPD [28] (Fig. 5C).