Unraveling the complexity of lipid body organelles in human eosinophils

Abstract

Lipid-rich organelles are common in many cell types. In cells, such as adipocytes, these organelles are termed LDs, whereas in other cells, such as leukocytes, they are called LBs. The study of leukocyte LBs has attracted attention as a result of their association with human diseases. In leukocytes, such as eosinophils, LB accumulation has been documented extensively during inflammatory conditions. In these cells, LBs are linked to the regulation of immune responses by compartmentalization of several proteins and lipids involved in the control and biosynthesis of inflammatory mediators (eicosanoids). However, it has been unclear how diverse proteins, including membrane-associated enzymes involved in eicosanoid formation, incorporate into LBs, especially if the internal content of LBs is assumed to consist solely of stores of neutral lipids, as present within adipocyte LDs. Studies of the formation, function, and ultrastructure of LBs in eosinophils have been providing insights pertinent to LBs in other leukocytes. Here, we review current knowledge of the composition and function of leukocyte LBs as provided by studies of human eosinophil LBs, including recognitions of the internal architecture of eosinophil LBs based on 3D electron tomographic analyses.

Lipid droplets in leukocytes: Organelles linked to inflammatory responses

“…However, during in vivo inflammatory diseases, there is an accentuated and rapid accumulation of LDs within these cells. LDs biogenesis is well documented both in vitro and in vivo in response to inflammatory stimuli and diseases (reviewed in [1, 2, 15]). For instance, increased LDs numbers are observed during acute respiratory distress syndrome [16] and allergic inflammation [17] in humans.…”

“…For example, platelet activating factor (PAF), through its receptor, induces LD formation in neutrophils and eosinophils [9, 20] while the chemokines CCL11 and CCL5, acting via CCR3 receptors, stimulate LD formation in eosinophils and basophils [11]. Numerous stimuli, listed in other reviews [2, 4] are now recognized to trigger LD formation in leukocytes.…”

“…1). These enzymes include the major AA-converting enzymes 5-lipoxygenase, 15-lipoxygenase, 5-lipoxygenase-activating protein, cyclooxygenase-2 and LTC 4 synthase (reviewed in [4, 39]).…”

“…Particularly, LDs reside in the leukocyte cytoplasm as highly dynamic stations able to change their composition in response to inflammatory events. A plethora of studies have been describing human inflammatory diseases and experimental inflammatory stimuli that elicit LD formation in leukocytes (reviewed in [1-4]).…”

Eosinophilia: a pragmatic approach to diagnosis and treatment

“…14,15 In addition to the granule proteins, a wide array of cytokines and chemokines are stored preformed in the secondary granules and can be secreted in response to specific signals, leading to the recruitment and activation of other cells involved in the inflammatory response, including lymphocytes, mast cells, and fibroblasts. 16,17 Eosinophil activation also leads to secretion of reactive oxygen intermediates and the formation of increased numbers of lipid bodies, the primary site of synthesis of eicosanoids, inflammatory mediators that include leukotriene C4 and 5-lipoxygenase. 18 …”