TNF and alpha 1-antitrypsin deficiency: In conclusion, Z-AAT accumulation in alveolar macrophages is a main driver for excessive neutrophils in pulmonary alveoli of AATD individuals by inducing the expression of CXCL-8 and TNFα in the cells and, in addition to a low concentration of extracellular AAT, further exacerbates neutrophil burden in the individuals.