Since S100A8 is normally expressed in circulating but not interstitial neutrophils [58], a possible explanation for the differential S100A8 levels is that B6-CF neutrophils do not properly recognize or transition to the resident milieu of the CF lung, or their mechanism of suppression may be compromised; thereby, B6-CF neutrophils fail to properly down-regulate S100A8 expression once they leave circulation and enter the lung interstitium, which may constitute a basic defect of the neutrophils or lung in the absence of CFTR function. This evidence concerns the gene S100A8 and cystic fibrosis.