Abstract
To determine the pathophysiology of the retinoic acid syndrome which occurs during all-trans-retinoic acid (ATRA) treatment of acute promyelocytic leukaemia patients, we investigated the direct effects of ATRA on the function of human neutrophils. We found that ATRA (10-200 microM) dose-dependently stimulated superoxide (O2-) generation in intact neutrophils. The maximal activity of ATRA-stimulated O2- generation was 3.0 nmol/min/10(6) cells. Adding EGTA to the assay mixture did not affect the activity nor was the intracellular free calcium concentration changed upon stimulation. The treatment of neutrophils with 0.1 microM staurosporine, an antagonist of protein kinase C, for 10 min, enhanced the activity of ATRA-stimulated O2- generation up to 186% of that for control samples. Wortmannin (1 microM), an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), reduced this stimulatory activity by 67%. These results suggest that ATRA activates the signalling pathway related to PI 3-kinase rather than that utilizing calcium and protein kinase C. ATRA enhanced the O2- generated in a sodium-dodecyl-sulphate (SDS) cell-free system, resulting in rates up to 288% higher than that seen with SDS alone. This enhancement was not affected...Continue Reading
Citations
Jan 6, 2007·Annals of Hematology·Jeddi RamziMeddeb Balkis
Dec 26, 2009·International Journal of Hematology·Mariko TanakaShinya Kimura
Aug 10, 2000·Clinical and Laboratory Haematology·K S CharlesJ T Reilly
Jan 25, 2005·International Journal of Dermatology·Yasser Abou MouradZiad Salem
Jun 9, 2005·Internal Medicine·Daisuke ShimizuMasafumi Taniwaki
Feb 9, 2011·Leukemia Research·Sanjeev K SharmaManoranjan Mahapatra
Jul 25, 2000·Journal of the American Academy of Dermatology·A C EsserA N Sapadin
Nov 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Scott GettingerMichael Grossbard
Apr 1, 2004·American Journal of Hematology·Keechilat PavithranMathew Thomas
May 23, 2018·Special Care in Dentistry : Official Publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry·M P BuligonK L Ferrazzo
Jan 7, 1999·FEBS Letters·H NishiokaT Kita
Jul 9, 2014·Infection and Immunity·Gabriel CabreraMarina S Palermo
Apr 19, 2008·Pediatric Blood & Cancer·Rahul NaithaniM Mahapatra
Mar 8, 2014·International Journal of Dermatology·Julia RigantiRicardo L Galimberti
Jul 16, 2005·Pediatric Hematology and Oncology·Selma UnalGönül Hiçsönmez