Abstract
Eosinophils and secretory leukocyte protease inhibitor (SLPI) are both associated with Th2 immune responses and allergic diseases, but whether the fact that they are both implicated in these conditions is pathophysiologically related remains unknown. Here we demonstrate that human eosinophils derived from normal individuals are one of the major sources of SLPI among circulating leukocytes. SLPI was found to be stored in the crystalline core of eosinophil granules, and its dislocation/rearrangement in the crystalline core likely resulted in changes in immunostaining for SLPI in these cells. High levels of SLPI were also detected in blood eosinophils from patients with allergy-associated diseases marked by eosinophilia. These include individuals with eosinophilic granulomatosis with polyangiitis (EGPA) and atopic dermatitis (AD), who were also found to have elevated SLPI levels in their plasma. In addition to the circulating eosinophils, diseased skin of AD patients also contained SLPI-positive eosinophils. Exogenous, recombinant SLPI increased numbers of migratory eosinophils and supported their chemotactic response to CCL11, one of the key chemokines that regulate eosinophil migratory cues. Together, these findings suggest a role for SLPI in controlling Th2 pathophysiologic processes via its impact on and/or from eosinophils.
Highlights
Eosinophils are one of the principal cellular components of the host response to helminth infection and participate in several allergy-associated inflammatory diseases, such as eosinophilic granulomatosis with polyangiitis (EGPA) and atopic dermatitis (AD)
The detection of eosinophils in the granulocyte fraction was based on high granularity revealed by the high side scatter parameter (SSC), and low/negative CD16 surface expression, whereas neutrophils were identified on the basis of lower SSC and CD16-positive staining Figure 1A)
secretory leukocyte protease inhibitor (SLPI) has been shown to act as an antiinflammatory molecule in myeloid cells such as macrophages and DCs [12], the role of this protein in granulocytes is much less defined
Summary
Eosinophils are one of the principal cellular components of the host response to helminth infection and participate in several allergy-associated inflammatory diseases, such as eosinophilic granulomatosis with polyangiitis (EGPA) and atopic dermatitis (AD). There are no reported cases of congenital eosinopenia in humans, whereas infection with parasites or allergic hypersensitivity is commonly associated with an often dramatic rise in blood or tissue eosinophil counts [1, 2]. These data suggest that eosinophils are evolutionarily beneficial, specific functions of eosinophils in immunity remain elusive. This is partly due to the phenotypic and functional differences between human and mouse eosinophils, which limit the usage of eosinophil-deficient experimental models in order to delineate eosinophil contributions to human health and disease mechanistically [1]
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