Ultrastructural immunogold localization of tumor necrosis factor-alpha to the matrix compartment of eosinophil secondary granules in patients with idiopathic hypereosinophilic syndrome.

Abstract

Peripheral blood eosinophils from two normal donors and two patients with the hypereosinophilic syndrome (HES) were analyzed with a post-embedding immunogold method to

Mechanisms of eosinophil cytokine release

“…The first cytokine found within lipid bodies was tumor necrosis factor-alpha (TNF-α). TNF-α was detected within cytoplasmic lipid bodies of several cell types present on colonic Crohn's disease biopsies, including infiltrating eosinophils (Beil et al 1993). Recently, TNF-α was also found within lipid bodies of circulating neutrophils of septic patients and murine infiltrating neutrophils of experimentally induced sepsis (Pacheco et al 2002).…”

“…Cytoplasmic lipid bodies of isolated human lung mast cells contain the basic fibroblast growth factor (bFGF), also found within mast cell secretory granules . Specifically within eosinophils, the presence of TNF-α (Beil et al 1993) and the lymphocyte chemoattractants RANTES and IL-16 has been detected at lipid bodies. It is noteworthy that TNF-α, RANTES and IL-16 are largely stored within eosinophil specific granules.…”

“…In addition to these toxic proteins, eosinophil specific granules also store at least two-dozen of pre-formed cytokines and chemokines with pro-inflammatory or immunoregulatory properties. By a variety of techniques, such as subcellular fractionation, immunogold electron microscopy, and immunocytochemistry, a growing list of cytokines has been found within human eosinophil granules, including: (a) prototypical Th1 cytokines: IL-12 (Grewe et al 1998) and IFN-γ (Lamkhioued et al 1996); (b) prototypical Th2 cytokines: IL-4 (Moller et al 1996b), IL-5 (Dubucquoi et al 1994, Moller et al 1996a, Desreumaux et al 1998) and IL-13 (Woerly et al 2002); (c) chemokines: RANTES , Ying et al 1996, IL-8 (Braun et al 1993), and eotaxin (Nakajima et al 1998); (d) growth factors: granulocyte/macrophage colony-stimulatin factor (GM-CSF) (Levi-Schaffer et al 1995, Desreumaux et al 1998, IL-3 (Desreumaux et al 1998), vascular endothelial growth factor (VEGF) (Horiuchi & Weller 1997), transforming growth factor (TGF)-α (Egesten et al 1996) and stem cell factor (SCF) (Hartman et al 2001); (e) pro-inflammatory cytokines: tumor necrosis factor (TNF)-α (Beil et al 1993) and Financial support: NIH grants (AI20241, AI22571, and HL-56386) (Lacy et al 1998); and (f) immune-regulators: IL-16 , IL-2, and IL-10 (Woerly et al 1999).…”

Eosinophil lysis and plasma extravasation

“…For example, it may not be trivial whether workers have given drugs, mediators, etc., intravenously or topically, on the airway mucosa. ERJEFÄLT et al [4], thus, found that topical L-NAME produced a potent exudative response that could not be mimicked by intravenous L-NAME. In the work that prompted the editorial by KUBES [2], only intravenous injections were employed [5].…”

A Gel-Based Dual Antibody Capture and Detection Method for Assaying of Extracellular Cytokine Secretion: EliCell

“…Most, if not all, of the cytokines found preformed within eosinophils have been localized to specific granules (4)(5)(6)(7)(8)(9). Strong evidence provided mainly through electron microscopic analyses suggests that the mobilization of these factors from granule stores and subsequent extracellular release follows a process termed "piecemeal" degranulation (PMD), where small cytokine-containing vesicles traffic from granules to the plasma membrane.…”