SPHK1 and chronic obstructive pulmonary disease: Taken together with our previous report of a cigarette smoke-induced inhibition of SPHK1 activity and an exogenous S1P-facilitated improvement in phagocytic function in THP-1 macrophages, our data suggest that the down-regulation of Spns2 and consequent decrease of S1P export from the bronchial epithelium in COPD and in response to cigarette smoke may affect alveolar macrophage phagocytic activity via insufficient S1P receptor signaling.