Regulation of ICAM‐3 and other adhesion molecule expressions on eosinophils <i>in vitro</i>. Effects of dexamethasone

Vilardell, Carme; Yagüe, Jordi; Mullol, Joaquim; Roca‐Ferrer, Jordi; Fuentes, Mireya; Perez, M.; Picado, César; Juan, Manel

doi:10.1034/j.1398-9995.1999.00251.x

Cited by 18 publications

(12 citation statements)

References 22 publications

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“…[53][54][55][56][57] In our hands, dexamethasone inhibited agonist-induced intracellular translocation, mobilization, and cell surface up-regulation of CD63. It also down-regulated agonistinduced ␤-hex release.…”

Section: Cd63 Mobilization In Human Eosinophils 4045mentioning

confidence: 99%

Translocation of the tetraspanin CD63 in association with human eosinophil mediator release

Mahmudi‐Azer

Downey

Moqbel

2002

Blood

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The tetraspanin CD63 (also known as LAMP-3) has been implicated in phagocytic and intracellular lysosome-phagosome fusion events. It is also present in eosinophils, with predominant expression on crystalloid granule membrane. However, its role in eosinophil function is obscure. We hypothesized that CD63 is associated with intracellular events involved in eosinophil activation and mediator release. We used a combination of confocal immunofluorescence microscopy, flow cytometry, and secretion assays, including ␤-hexosaminidase, eosinophil peroxidase, and RANTES, to examine CD63 expression, intracellular localization, and its association with cell activation and mediator release. In resting eosinophils, CD63 immunoreactivity was localized to plasma and crystalloid granule membranes. In interferon-␥ (IFN-␥)-or C5a/CB-stimulated cells (10 minutes), intracellular CD63 appeared to shift to the cell periphery and plasma membrane, while stimulation with a cocktail of interleukin-3 (IL-3)/IL-5/granulocyte-macrophage colony-stimulating factor induced the appearance of discrete intracellular clusters of CD63 immunoreactivity. IFN-␥ induced mobilization of CD63 to the cell periphery, which coincided with selective mobilization of RANTES prior to its release, implying CD63 association with piecemeal degranulation. Agonist-induced CD63 mobilization and cell surface upregulation was associated with ␤-hexosaminidase, eosinophil peroxidase, and RANTES release. Dexamethasone as well as genistein (a broad-spectrum inhibitor of tyrosine kinases) inhibited agonistinduced intracellular mobilization of CD63 and RANTES together with cell surface up-regulation of CD63 and mediator release. This is the first report of an association between CD63 mobilization and agonist-induced selective mediator release, which may imply the involvement of CD63 in eosinophil activation and piecemeal degranulation. IntroductionEosinophils are major effector cells in allergic inflammation and asthma. 1-3 They synthesize, store, and release a wide range of proinflammatory mediators, including at least 4 cationic proteins 1,2 and up to 23 cytokines and growth factors. 4,5 Eosinophils contain different populations of mediator-storage organelles, including small secretory vesicles as well as crystalloid granules. The latter secretory granules are the site of storage of cytotoxic cationic proteins as well as a number of cytokines, chemokines, and growth factors. 6,7 The membrane-bound crystalloid granule comprises 2 compartments: an electron-dense crystalline core (internum) where major basic protein (MBP) 8,9 is stored and an electron-lucent matrix 6 where 3 cationic proteins-namely, eosinophil cationic protein, eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin 1,8 -together with a number of other cytokines, including interleukin-6 (IL-6) 10 and RANTES (regulated on activation normal T cells expressed and secreted), 11 are stored. Among eosinophilderived mediators, ␤-hexosaminidase (␤-hex) has been shown to localize to both small secretory vesicle...

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Section: Cd63 Mobilization In Human Eosinophils 4045mentioning

confidence: 99%

Translocation of the tetraspanin CD63 in association with human eosinophil mediator release

Mahmudi‐Azer

Downey

Moqbel

2002

Blood

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“…This occurs through downregulation of leukocyte adhesion molecules, such as leukocyte factor adhesion-1 (LFA-1) and L-selectin (possibly via direct modulation of lipocortin 1 by glucocorticoids), and endothelial adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), as well as through inhibition of chemokine release (IL-8 and other cysteine-X-cysteine chemokines) by immune accessory cells at inflamed sites [10][11][12]. Similarly, glucocorticoids may block eosinophil transmigration through inhibition of adhesion molecules, such as ICAM-3, and the release of chemokines, such as eotaxin and other cysteine-cysteine-type compounds [13,14].…”

Section: Innate Immunitymentioning

confidence: 99%

Glucocorticoids and Inflammation Revisited: The State of the Art

Franchimont

Kino²,

Galon³

et al. 2002

Neuroimmunomodulation

118

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Glucocorticoids have been used in the treatment of inflammatory and autoimmune diseases and to prevent graft rejection for over 50 years. These hormones exert their effects through cytoplasmic, heat shock protein-bound glucocorticoid receptors that translocate into the nucleus, where they regulate the transcriptional activity of responsive genes by binding to specific promoter DNA sequences (transactivation) or by interacting with transcription factors (transrepression). By interacting with different signaling pathways, newly characterized nuclear receptor coregulators enhance or diminish the actions of glucocorticoids, thus explaining the gene-, cell-, tissue- and context-dependent actions of glucocorticoids. Glucocorticoids modulate genes involved in the priming of the innate immune response, while their actions on the adaptive immune response are to suppress cellular [T helper (Th)1-directed] immunity and promote humoral (Th2-directed) immunity and tolerance. The past decade has produced new insights into the mechanisms of glucocorticoid sensitivity and resistance of inflammatory, autoimmune and allergic diseases. Both the quality and severity of the inflammatory stimulus, as well as the genetics and constitution of the patient, play key roles in the glucocorticoid sensitivity, dependency and resistance of these diseases. Although glucocorticoids increase susceptibility to opportunistic infections, they are also highly beneficial in the presence of serious systemic inflammation, such as that observed in septic shock and acute respiratory distress syndrome, when administered in a sustained fashion throughout the course of the disease. Glucocorticoids produce their cardiovascular, metabolic and antigrowth side effects through molecular mechanisms distinct from those involved in immunomodulation. Fortunately, the first generation of tissue- and immune- versus cardiovascular/metabolic effect-selective glucocorticoids is available for study and further improvement. ‘Designer’ glucocorticoids promise to be a great new advance in the therapy of inflammatory diseases.

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“…All leukocyte subgroups express β2 integrins such as LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and P150,95 (CD11c/CD18), which interact with the members of immunoglobulin supergene family on endothelial cells such as ICAM-1 and ICAM-2 (Weller et al 1991;Kroegel et al 1994;Juan et al 1999;Jia et al 1999). Whereas eosinophils adhere to VCAM-1 spontaneously, they need an activation signal to bind to ICAM-1 (Nagata et al 1998).…”

Section: Endothelium-dependent Eosinophil Activation and Firm Adhesionmentioning

confidence: 99%

“…Lselectin mAb only weakly inhibits the adhesion of eosinophils to mesenteric endothelial cells (Sriramarao et al 1994). This may be because eosinophils express Lselectin, but to a lower extent than neutrophils (Patel and McEver 1997;Juan et al 1999). L-selectin can also mediate intercellular interactions between leukocytes (Ikegami-Kuzuhara et al 2001).…”

Section: Introductionmentioning

confidence: 97%

Vascular adhesion and transendothelial migration of eosinophil leukocytes

Gönlügür

Efeoglu

2004

Cell Tissue Res

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Tissues respond to injury with inflammation in an effort to protect and repair the damaged site. During inflammation, leukocytes typically accumulate in response to certain chemicals produced within the tissue itself. The passage of leukocytes through the vascular lumen into tissues occurs in several phases, including rolling, activation, firm adhesion, transendothelial migration, and subendothelial migration. Although infiltration of eosinophil leukocytes is one of the most important aspects of allergic inflammatory reactions, eosinophils also participate in nonallergic inflammation. Eosinophil accumulation is regulated not only by endothelial adhesion molecules, but also by interactions between eosinophil adhesion molecules and extracellular matrix elements. This review summarizes the regulation of eosinophil leukocyte adhesion and migration. A better understanding of eosinophil recruitment responses may lead to the development of novel therapeutics for chronic allergic diseases.

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Regulation of ICAM‐3 and other adhesion molecule expressions on eosinophils in vitro. Effects of dexamethasone

Cited by 18 publications

References 22 publications

Translocation of the tetraspanin CD63 in association with human eosinophil mediator release

Translocation of the tetraspanin CD63 in association with human eosinophil mediator release

Glucocorticoids and Inflammation Revisited: The State of the Art

Vascular adhesion and transendothelial migration of eosinophil leukocytes

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Regulation of ICAM‐3 and other adhesion molecule expressions on eosinophils in vitro. Effects of dexamethasone

Cited by 18 publications

References 22 publications

Translocation of the tetraspanin CD63 in association with human eosinophil mediator release

Translocation of the tetraspanin CD63 in association with human eosinophil mediator release

Glucocorticoids and Inflammation Revisited: The State of the Art

Vascular adhesion and transendothelial migration of eosinophil leukocytes

Contact Info

Product

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Regulation of ICAM‐3 and other adhesion molecule expressions on eosinophils in vitro. Effects of dexamethasone