Interaction of SDF-1α and CXCR4 plays an important role in pulmonary cellular infiltration in differentiation syndrome

This study aims to investigate the role of stromal cell-derived factor 1α (SDF-1α) and its receptor CXCR4 in cellular infiltration of the lung in differentiation syndrome (DS). The acute promyelocytic leukemia (APL) NB4 cells and freshly prepared APL cells from the patients were differentiated by all-trans retinoic acid (ATRA). The expression of SDF-1α in human lung tissues was examined by RT-PCR and Western blot analysis. The cells were subjected to adhesion, migration or invasion assays, and co-cultured with human lung tissues in a microgravity rotary cell culture system to examine cellular infiltration in situ. ATRA-differentiated cells expressed high levels of CXCR4, and adhered more strongly to matrigel. Their ability to migrate and invade was enhanced by SDF-1α and lung homogenate, and diminished by pre-treatment with an anti-CXCR4 blocking antibody. SDF-1α was expressed in the lung tissues of all seven human donors. ATRA-differentiated NB4 cells infiltrated into lung tissues, and this was reduced by pre-treatment with an anti-CXCR4 blocking antibody. The interaction of SDF-1α and CXCR4 plays an important role in pulmonary cellular infiltration during DS, suggesting that targeting SDF-1α and CXCR4 may provide the basis for potential treatments in the management of DS.