Nitric oxide regulates endotoxin-induced TNF-alpha production by human neutrophils.

Abstract

We studied the effect of nitric oxide on LPS-induced TNF-alpha production by human neutrophils. Human neutrophils exposed to LPS and IFN-gamma did not show measurable increases in intracellular cyclic GMP (cGMP). However, cGMP increased upto 30-fold (p < 0.01) in neutrophils incubated with both sodium nitroprusside (SNP), an exogenous source of nitric oxide, and N-acetylcysteine (NAC), which increases the bioavailability of nitric oxide; this increase indicates that neutrophils contain a nitric oxide-sensitive guanylate cyclase. SNP, with or without NAC, did not increase TNF-alpha production in human neutrophils cultured in medium alone. However, LPS-dependent TNF-alpha production was increased by exposure to SNP (p < 0.05); this effect was further increased by the addition of NAC (p < 0.02). IFN-gamma greatly increased LPS-mediated TNF-alpha production by human neutrophils (p < 0.01), and SNP plus NAC was found to further augment this production (p < 0.01). The up-regulation of TNF-alpha production by nitric oxide was not associated with increased amounts of LPS-induced TNF-alpha mRNA, and was not reproduced by exposing neutrophils to cGMP analogues. These data suggest that nitric oxide released by endothelial and vascular smooth muscle cells may exert a paracrine effect on human neutrophils and augment the inflammatory response in sepsis by increasing the production of cytokines. Although the mechanism of this effect remains unknown, it does not seem to be dependent on cGMP or increased levels of TNF-alpha mRNA.

Effect of nitric oxide supply on the morphofunctional state of the lungs during cardiopulmonary bypass modelling: an experimental study

“…NO применяется как легочный вазодилататор, при его доставке отмечается улучшение V / Q, оксигенации и снижение постнагрузки правого желудочка [24]. NO обладает бронходилатирующим эффектом [25], при этом снижается сопротивление дыхательных путей, улучшается вентиляция легких, что позволяет не только оптимизировать V / Q, но и уменьшить синтез провоспалительных цитокинов [26], ингибировать адгезию, миграцию нейтрофилов и моноцитов в ткань за счет уменьшения количества поверхностных молекул адгезии, ограничить секвестрацию нейтрофилов [27] и агрегацию тромбоцитов [24]. NO ингибирует перекисное окисление липидов, а также может напрямую поглощать АФК [24].…”

Roles of Nitric Oxide in Surgical Infection and Sepsis

“…Through tissue damage, NO or ONOO Ϫ promotes inflammatory changes, but there is also evidence that NO may regulate and promote inflammatory cytokine synthesis independent of tissue injury. NO enhances TNF and IL-8 release [83,84] and activates cyclooxygenase, increasing formation of proinflammatory prostaglandins [13]. Conversely, NO may also play an antiinflammation role.…”

Delivery exogenous nitric oxide via cardiopulmonary bypass in pediatric cardiac surgery reduces the duration of postoperative mechanical ventilation-A meta-analysis of randomized controlled trials

“…The nitric oxide (NO) pathway is a major component of this process. NO could regulate cell apoptosis, and played an active role in inhibiting platelet adhesion and aggregation, Monocyte adhesion, migration and production of oxygen free radicals [ [10] , [11] , [12] , [13] ]. Previous study have shown NO plays a variety of protective roles in inflammatory response, ischemia/reperfusion injury and cell apoptosis [ 14 ].…”