Neutrophils, key cells of the innate immune system, are still regarded as a relatively homogeneous cell population with minimal discernible phenotypic and functional diversity. Amongst the reasons for this misconception is the fact that neutrophils are still largely defined by their morphology. In comparison, other immune cells, such as lymphocytes and macrophages, are now well known to form distinct subsets that differ morphologically and phenotypically. Recently, there has been a paradigm shift in the understanding of neutrophil diversity. The identification of low density neutrophils (LDN), a subpopulation of neutrophils initially described in patients with rheumatic diseases, has begun a new era in neutrophil biology research. The aim of this review paper is to describe LDNs in the context of a number of pathological and physiological conditions including systemic lupus erythematosus (SLE), cancer, human immunodeficiency virus (HIV), sepsis, asthma, and pregnancy. Within the context of each condition, this paper will discuss briefly the techniques used to isolate and characterize LDNs while focusing on the phenotype, function, proposed origin and physiological development of LDNs in each condition.
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