Nonhematopoietic NADPH oxidase regulation of lung eosinophilia and airway hyperresponsiveness in experimentally induced asthma

Abstract

Cook-Mills JM. Nonhematopoietic NADPH oxidase regulation of lung eosinophilia and airway hyperresponsiveness in experimentally induced asthma.

Endothelial cell PTP1B regulates leukocyte recruitment during allergic inflammation

“…These data are consistent with our previous reports that in vitro, endothelial cell PTP1B is a mediator of VCAM-1 signaling (16) and reports that VCAM-1 is required for infiltration of eosinophils in response to OVA challenge to the lung (12). This is also consistent with our previous report in which chimeric mice with a deficiency in nonhematopoietic NADPH oxidase 2 (NOX2), a VCAM-1 signal upstream of PTP1B, had accumulation of eosinophils on the endothelium and reduced eosinophils in the lung without altering lung adhesion molecules, cytokines, or chemokines (4).…”

An Antibody to the Sixth Ig-like Domain of VCAM-1 Inhibits Leukocyte Transendothelial Migration without Affecting Adhesion

“…In summary, VCAM-1-D6 Ab, which is reactive to VCAM-1 domain 6, inhibits transmigration but not adhesion, suggesting that the sixth IgG-like domain may participate in transmigration (36,50).…”

“…Leukocyte binding to adhesion molecules, including VCAM-1, activates signals within endothelial cells that allow the opening of narrow vascular passageways between endothelial cells or through an individual endothelial cell for transendothelial migration (34)(35)(36)(37)(38)(39). When endothelial cell adhesion molecule signaling is inhibited, leukocytes bind to the endothelium, but transendothelial migration does not occur (40), and leukocytes are often released from the endothelium to continue in the blood flow (41,42).…”

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

“…For example, infection of gp91phox−/− mice with the yeast C. neoformans or with influenza virus was in either case found to result in increased Th1-skewed inflammation and granuloma formation, compared to their wild-type counterparts, which led to increased influenza clearance and protection against C. neoformans infection (204,205). Studies using chimera of gp91phox−/− mice indicated a contribution of non-hemapoetic cell NADPH oxidase to development of airways eosinophilia in a mouse model of allergic inflammation, suggesting a role for NOX2 within the vascular endothelium (206). Studies with gp91phox−/− mice also indicated a role for NOX2, presumbly within the endothelium, in development of pulmonary arterial hypertension in response to chronic hypoxia (176).…”