Role of Nitric Oxide in Neutrophil Maturation and Function

Abstract

Five year ago, when I started my PhD on neutrophils after completing my Master’s in Plant Biotechnology. I considered this cell an innate immune phagocyte as every student read in immunology books by Kuby and Roitt. However, when I started reviewing the literature I found a remarkable upswing in interest in this cell in the last decade. This cell had generated a lot of interest by interlinking innate and specific immune responses. The last five years have witnessed even more remarkable new research in the field of neutrophil biology like antigen presentation, NETs formation, anti- inflammatory microparticle release and cross talk with B and T cells. Nitric oxide a signaling molecule has an unending list of functions that depends on its concentration, proximity and redox state and also modulates neutrophil function. The work described in this dissertation was carried out between July 2004 and July 2009 at the Central Drug Research Institute, Lucknow under the able guidance of Dr. Madhu Dikshit, Head CVS Unit, Pharmacology Division. In preparing this monograph thesis I tried to pursue two major aims. First, to provide a detail overview of recent development in neutrophil biology, and effect of NO/NOS on neutrophil functions in the review of literature section. Second to present own research on this cell in detail and to discuss the outcomes and possibilities of future. In the present monograph the detailed exploration of NOS isoforms in neutrophils and its precursor cells from bone marrow is done and documented. Functional studies like NO mediated free radical generation and NETs formation were also carried out. Moreover effect of NO on the proliferation and apoptosis of promyelocytic cell line HL-60 was explored in detail. As recent research suggest, NO as a modulator of hematopoiesis, the NO derived from the precursor cells in bone marrow could add substantial amount of NO in the bone marrow niche and this might be playing a key role in hematopoiesis which needs further exploration