Nitric oxide regulates human eosinophil adhesion mechanisms in vitro by changing integrin expression and activity on the eosinophil cell surface

Abstract

1 The nitric oxide synthase (NOS) inhibitor, N o -nitro-L-arginine methyl ester (L-NAME), inhibits both rat and human eosinophil chemotaxis in vitro. Here, the role of nitric oxide (NO) in human eosinophil cell surface integrin expression and function was investigated. 2 Human peripheral blood eosinophils were treated with L-NAME (0.01 ± 1.0 mM) and their adhesion to human ®bronectin and serum observed. Adhesion of cells to ®bronectin and serum increased by 24.0+4.6 and 43.8+4.7%, respectively, when eosinophils were treated with 1.0 mM L-NAME. Increased adhesion by L-NAME could be abolished when cells were co-incubated with VLA-4-and Mac-1-speci®c monoclonal antibodies (mAbs). 3 The NO donor, sodium nitroprusside (2.5 mM), signi®cantly inhibited eosinophil adhesion to ®bronectin and serum by 34.3+4.5 and 45.2+5.6%, respectively. This inhibition was accompanied by a 4 fold increase in the levels of intracellular cyclic GMP. 4 Flow cytometrical analysis demonstrated that L-NAME induced an increased expression of CD11b (Mac-1) on the eosinophil cell surface of 36.3+7.4%. L-NAME had no eect upon CD49d (VLA-4) expression. 5 Treatment of human eosinophils, in vitro, with H-[1,2,4] oxadiazolo quinoxalin-1-one (ODQ) (0.1 mM), an inhibitor of soluble guanylate cyclase, also signi®cantly increased eosinophil adhesion to ®bronectin and serum by 73.5+17.9 and 91.7+12.9%, respectively. This increase in adhesion could also be inhibited by co-incubation with the Mac-1 and VLA-4-speci®c mAbs. 6 In conclusion, results indicate that NO, via a cyclic GMP-dependent mechanism, inhibits the adhesion of human eosinophils to the extracellular matrix (ECM). This inhibition is accompanied by a decrease in the expression and function of the eosinophil's adhesion molecules, in particular, the expression of the Mac-1 integrin and the function of the VLA-4 integrin.

Comparative study of eosinophil chemotaxis, adhesion, and degranulation in vitro in ulcerative colitis and Crohnʼs disease

“…22,32 For example, PMA (a protein kinase C activator) generally promotes adhesion by targeting events that occur following receptor occupancy without significantly affecting the affinity of the receptor for the ligand. 34 Eosinophil adhesion to fibronectin is mediated by VLA-4, 35 which plays an important role in the selective accumulation of eosinophils into inflamed tissue. Moreover, PAF stimulates human eosinophil adherence to fibronectin-coated plates.…”

A Nitric Oxide-Releasing Salbutamol Elicits Potent Relaxant and Anti-Inflammatory Activities

“…However, other studies suggest that constitutional NOS-derived NO and not inducible NOS-derived NO may be pro-inflammatory (Nevin and Broadley, 2002). In contrast, NO may also reduce leukocyte chemotaxis (Kuo et al, 1997) and adherence of leukocytes to the vascular endothelial cell wall (Conran et al, 2001). Inducible NOS-deficient mice that were treated with endotoxin showed enhanced leukocyte accumulation in lung tissue compared with wild-type mice similarly treated with endotoxin (Hickey et al, 1997).…”

Acute hemolytic vascular inflammatory processes are prevented by nitric oxide replacement or a single dose of hydroxyurea

“…Although in vivo data indicate that the ability of HU to abrogate hemolytic inflammation may primarily be the result of its ability to counteract the immediate depletion of NO by Hb, HU may also diminish the subsequent effects that Hb has on leukocyte and endothelial activation, potentially reducing the ability of the endothelium to capture and tether leukocytes in response to Hb or its products and reducing the subsequent ability of neutrophils to firmly adhere to endothelial ICAM-1. [49][50][51] Given that ongoing clinical trials demonstrate potential for the use of pan-selectin inhibitors for Figure 7. HU reverses the effects of Hb on endothelial cell activation and neutrophil adhesion in vitro.…”