MCP-1 in the migration of differentiated leukemic cells toward alveolar epithelial cells

¹ Depts of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Hematology and Oncology, Dept of Medicine and; and Dept of Respiratory Therapy, Taipei Medical University, Taipei, Taiwan
² Dept of Respiratory Therapy, Taipei Medical University, Taipei, Taiwan
³ Dept of Medical Research and Education, Taipei-Veterans General Hospital, Taipei, Taiwan
⁴ Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
⁵ Depts of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Hematology and Oncology, Dept of Medicine and; and Dept of Medicine, Taipei City Hospital-Yang-Ming Branch, Taipei, Taiwan, Republic of China

^* To whom correspondence should be addressed. E-mail: hchsu{at}vghtpe.gov.tw.

	Abstract

All-trans retinoic acid (ATRA) can induce acute respiratory distress syndrome in patients with acute promyelocytic leukemia (APL). We investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the chemotactic transmigration of ATRA-treated NB4 (ATRA-NB4) APL cells toward A549 alveolar epithelial cells.

NB4 and A549 cells were separately cultured with ATRA and/or dexamethasone. ATRA-NB4 cells were then placed in an upper insert and co-incubated with A549 cells or their conditioned medium (CM) located in a lower plate to test their transmigration activity.

ATRA stimulated NB4 cells to transmigrate toward the A549 cells. The secretion of MCP-1 was enhanced by ATRA treatment in both A549 and NB4 cells. The binding assay demonstrated that ATRA-NB4 cells bound MCP-1. Both pretreatment of CM-A549 cells with antibodies against MCP-1 and pretreatment of ATRA-NB4 cells with antibodies against MCP-1 receptors reduced ATRA-NB4 cell transmigration. Dexamethasone did not suppress MCP-1 secretion and transmigration in ATRA-NB4 cells, but when applied to A549 cells, MCP-1 secretion was suppressed and ATRA-NB4 cell transmigration was attenuated.

MCP-1 secreted from alveolar epithelial cells plays an important role in the cell-cell interaction involved in the chemotactic transmigration of ATRA-treated APL cells toward alveolar epithelial cells.