The effect of alpha 1 antitrypsin on phagocyte function

alpha 1 antitrypsin (alpha 1AT) deficiency is a common genetic variant associated with many immunological and inflammatory disorders. Previous studies in alpha 1 AT deficient subjects have indicated possible monocyte (MN) and neutrophil (PMN) abnormalities with enhanced chemiluminescence (CL) and accelerated delayed hypersensitivity reactions. We have therefore extended these observations by investigating the effect of purified alpha 1 AT on MN and PMN motility and CL. These studies indicated that alpha 1 AT in physiological amounts inhibits PMN and MN chemokinesis by about 35% but chemotaxis by only 10%. It however has no direct effect on the zymosan induced CL of these cells. This study suggests that the increased incidence and severity of some inflammatory diseases in alpha 1 AT deficient subjects may in part be explained by increased motility and activation of MN and PMN, the former due to the absence of an inhibitor of PMN and MN locomotion and the latter due to secondary changes in serum resulting in enhanced chemiluminescence.