Regulation of α4 integrin–mediated adhesion of human eosinophils to fibronectin and vascular cell adhesion molecule-1

Zhu

The Journal of Immunology

et al. 2001

We examined the role of p38, p42, and p44 mitogen-activated protein kinase (MAPK) isoforms and cytosolic phospholipase A2 (cPLA2) activation in human eosinophil adhesion to plate-coated fibronectin (FN). In the control state, eosinophil adhesion was maximal, with 10 μg/ml FN at 30 min, and decreased after 60–90 min. Western blot analysis demonstrated that p44/42 MAPK (extracellular signal-regulated kinase (ERK)1/2) and cPLA2 were phosphorylated during adhesion to FN, whereas p38 MAPK phosphorylation was unchanged. Preincubation of eosinophils with U0126 or PD98059, two structurally unrelated MAPK kinase inhibitors, or arachidonic trifluoromethyl ketone, a cPLA2 inhibitor, blocked eosinophil adhesion to FN. By contrast, eosinophil adhesion was unaffected by SB203580, a p38 MAPK inhibitor. Pretreatment of eosinophils with okadaic acid, a serine/threonine phosphatase inhibitor, at the concentrations that induced ERK1/2 and cPLA2 phosphorylation caused an increase in maximal eosinophil adhesion to FN for >60 min. MAPK kinase inhibition but not p38 inhibition also blocked FN-mediated F-actin redistribution in eosinophils and prevented cPLA2 phosphorylation caused by adhesion to FN. These results demonstrate that ERK1/2 mediating cPLA2 activation is essential for eosinophil adhesion to FN.

Section: Discussionsupporting

confidence: 68%

Extracellular Signal-Regulated Kinase 1/2-Mediated Phosphorylation of Cytosolic Phospholipase A2 Is Essential for Human Eosinophil Adhesion to Fibronectin

Zhu

The Journal of Immunology

et al. 2001

The Journal of Immunology

“…A tyrosine kinase inhibitor, genistein, but not tyrphostin B46, also showed a significant inhibitory effect. Genistein is reported to block ␤ 2 integrin-mediated eosinophil activation (74,75), whereas tyrphostin B46 blocks ␤ 1 integrin-mediated eosinophil adhesion (76). These results imply the involvement of some specific tyrosine kinase in CD30-mediated apoptosis.…”

Section: Discussionmentioning

confidence: 86%

Extremely Rapid and Intense Induction of Apoptosis in Human Eosinophils by Anti-CD30 Antibody Treatment In Vitro

Matsumoto

Terakawa

Miura

et al. 2004

Self Cite

Apoptosis is an important cellular mechanism for controlling cell viability and proliferation. With respect to eosinophils, cytokines prolong their survival, whereas corticosteroids reduce their survival in vitro. CD30, a member of the TNFR family, is expressed on the surface of many cell types, including Hodgkin’s lymphoma cells. CD30 is capable of inducing apoptosis after Ab treatment in some cell lines. To determine whether this surface structure is involved in apoptosis of human eosinophils, we examined its expression and the effect of anti-CD30 Ab treatment on the viability of eosinophils. Purified human eosinophils expressed low, but consistently detectable, levels of CD30. Immobilized, but not soluble, forms of anti-CD30 Abs (HRS-4 and Ber-H8) or recombinant mouse CD30 ligand exhibited an extremely rapid and intense survival-reducing effect on the eosinophils in the presence of exogenous IL-5; this effect was both concentration and time dependent. Furthermore, high concentrations of IL-5 could not reverse the reduced survival rates. After treatment with anti-CD30 Ab, gel electrophoresis of DNA extracted from the eosinophils demonstrated changes consistent with apoptosis. The immobilized F(ab′)2 of the anti-CD30 Ab failed to induce eosinophil apoptosis. The addition of anti-CD18 Ab also completely abrogated the induction of eosinophil apoptosis. Further examination using specific signal transduction inhibitors suggested the involvement of p38, mitogen-activated protein kinase kinase 1/2, and specific tyrosine kinase, but not NF-κB, in the induction of CD30-mediated eosinophil apoptosis. These data demonstrate that CD30 can modify eosinophil survival by causing an extremely rapid and intense induction of apoptosis through a tightly regulated intracellular signaling pathway.

“…However, these integrins bind to different counter-receptors and are regulated by distinct signals. IL-5, platelet-activating factor or RANTES treatment increased g 2 integrinmediated eosinophil adhesion, but not VLA-4-( § 4 g 1 integrin-) mediated cell adhesion [28]. The eosinophil chemokine, eotaxin, was reported to enhance [29] or suppress [30] adhesion of eosinophils to VCAM-1 in different experimental systems.…”

Section: Discussionmentioning

confidence: 94%

Superoxide activates very late antigen‐4 on an eosinophil cell line and increases cellular binding to vascular cell adhesion molecule‐1

et al. 2003

The recruitment of eosinophils to the airway is a key event in the pathogenesis of allergy. Very late antigen-4 (VLA-4), an integrin ligand for vascular cell adhesion molecule-1 (VCAM-1), is expressed on eosinophils. VLA-4-mediated adhesion of eosinophils to VCAM-1 may contribute to their selective recruitment to tissues in allergy. Reactive oxygen species (ROS), including nitric oxide (NO), are abundant in the airway of allergic patients, but their role in pathogenesis of allergy is unclear. In this investigation, we studied the effects of ROS on integrin-mediated eosinophil adhesion. Recombinant soluble VCAM-1 and ICAM-1 were used to test the effects of ROS on the integrin-mediated adhesion of an eosinophil cell line. We used phorbol 12-myristate 13-acetate-stimulated neutrophils and hypoxanthine to generate superoxide, NO donors as sources of NO, and a static cell-to-protein adhesion assay to analyze cellular adhesion. Stimulated neutrophils significantly increased eosinophil binding to VCAM-1, which was reversed in the presence of superoxide dismutase. Neutrophils from a chronic granulomatous disease patient lacked this activity in enhancing eosinophil adhesion. Our results suggest that the balance between ROS molecules in different tissue microenvironments may change the integrin-mediated leukocyte adhesion and is likely to be a key factor in leukocyte recruitment in allergic inflammation.