| First Author | Bhopale VM | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 28 | Pages | 17474-84 |
| PubMed ID | 26032418 | Mgi Jnum | J:223389 |
| Mgi Id | MGI:5648762 | Doi | 10.1074/jbc.M115.651620 |
| Citation | Bhopale VM, et al. (2015) Factors Associated with Nitric Oxide-mediated beta2 Integrin Inhibition of Neutrophils. J Biol Chem 290(28):17474-84 |
| abstractText | This investigation explored the mechanism for inhibition of beta2 integrin adhesion molecules when neutrophils are exposed to nitric oxide ((*)NO). Roles for specific proteins were elucidated using chemical inhibitors, depletion with small inhibitory RNA, and cells from knock-out mice. Optimal inhibition occurs with exposures to a (*)NO flux of approximately 28 nmol/min for 2 min or more, which sets up an autocatalytic cascade triggered by activating type 2 nitric-oxide synthase (NOS-2) and NADPH oxidase (NOX). Integrin inhibition does not occur with neutrophils exposed to a NOX inhibitor (Nox2ds), a NOS-2 inhibitor (1400W), or with cells from mice lacking NOS-2 or the gp91(phox) component of NOX. Reactive species cause S-nitrosylation of cytosolic actin that enhances actin polymerization. Protein cross-linking and actin filament formation assays indicate that increased polymerization occurs because of associations involving vasodilator-stimulated phosphoprotein, focal adhesion kinase, and protein-disulfide isomerase in proximity to actin filaments. These effects were inhibited in cells exposed to ultraviolet light which photo-reverses S-nitrosylated cysteine residues and by co-incubations with cytochalasin D. The autocatalytic cycle can be arrested by protein kinase G activated with 8-bromo-cyclic GMP and by a high (*)NO flux ( approximately 112 nmol/min) that inactivates NOX. |
