Retinoic acid - A player that rules the game of life and death in neutrophils

Neutrophils are the most prevalent white blood cells in the circulation. They represent the first line of defense against invading microorganisms and have been implicated in the pathogenesis of a number of human diseases. In response to various factors, the pluripotent stem cells in bone marrow differentiate into mature neutrophils, enter the blood stream, and die within 24 hr via apoptosis. Numerous defects can occur during the process of neutrophils' differentiation that can manifest in the form of a variety of clinical disorders. Retinoids (Vitamin A and analogues), in general, and all-trans retinoic acid (tRA), in particular, play a critical role during differentiation of neutrophils, tRA can directly modulate gene expression via binding to its nuclear receptors, which in turn, can activate transcription of genes that are essential for differentiation of immature cells to neutrophils. Involvement of retinoic acid receptor in pathogenesis of acute promyelocytic leukemia (APL), reflects an important role played by this receptor in differentiation of immature myeloid cells to neutrophils. This review summarizes evidence on involvement of retinoic acid-mediated events in differentiation process of neutrophils and their subsequent apoptosis.