l-NAME–induced neutrophil accumulation in rat lung is not entirely because of interactions with L- and P-selectins or CD18

Román, Ángela; McGahren, Eugene D.

doi:10.1016/j.jpedsurg.2006.05.062

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…In this study we demonstrate that in microvasculature of human skin, functional blocking of P- and E-selectins resulted in a decrease of rolling but not adhesion elicited by L-NAME. The interplay between endogenous NO and endothelial selectin expression remains unclear although previous studies show that inhibition of NO may enhance the expression of endothelial adhesion molecules including selectins [42,43]. E-selectin expression was previously shown to be modulated by L-NAME [44] an effect that may be mediated by NF-κB [45].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature

2012

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BackgroundNitric oxide (NO) is a multifunctional signaling molecule that regulates important cellular events in inflammation including leukocyte recruitment. Previous studies have shown that pharmacological inhibition of NO synthesis induces leukocyte recruitment in various in vitro and animal models. However, it is not known whether NO modulation has similar effects on leukocyte-endothelial cell interactions within the human microvasculature. The present study explored the effect of systemic L-NAME treatment on leukocyte recruitment in the SCID-hu mouse model.MethodsHuman skin xenografts were transplanted in SCID mice to study human leukocyte dynamics in human vasculature. Early events of human leukocyte recruitment in human vasculature were studied using intravital microscopy. NO synthesis was pharmacologically inhibited using NG-nitro-L-arginine methyl ester (L-NAME). Immunohistochemical analysis was performed to elucidate E-selectin expression in human xenograft skin. Human neutrophil-endothelial cell interactions were also studied in an in vitro flow chamber assay system. P- and E-selectin expression on cultured human umbilical vein endothelial cells (HUVECs) was measured using ELISA. Platelet-activating factor (PAF) synthesis was detected using a TLC-based assay.ResultsL-NAME treatment significantly enhanced the rolling and adhesion of human leukocytes to the human vasculature. Functional blocking of P- and E-selectins significantly inhibited rolling but not adhesion induced by inhibition of NO synthesis. Systemic L-NAME treatment enhanced E-selectin expression in human xenograft skin. L-NAME treatment significantly enhanced P- and E-selectin expression on HUVECs. L-NAME treatment did not significantly modify neutrophil rolling or adhesion to HUVECs indicating that L-NAME−induced subtle P- and E-selectin expression was insufficient to elicit dynamic neutrophil-HUVEC interactions in vitro. Moreover, synthesis of endothelial-derived PAF was not significantly modified by L-NAME treatment. These results point to the accelerated leukocyte recruitment in human vasculature following suppression of NO synthesis, effects that are mediated by P- and E-selectins. The findings are, however, not supported by the in vitro data.ConclusionInhibition of endogenous NO triggers early events of human leukocyte recruitment in human vasculature, involving complex cellular or molecular mechanisms in addition to P- and E-selectin-mediated leukocyte rolling.

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Section: Discussionmentioning

confidence: 99%

Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature

2012

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“…This induced increase in rolling is P- and E-selectin-dependent 124 . Likewise, eNOS knockout mice showed an increased expression of P-selectin 125 . Leukocyte rolling and adhesion in mesenteric venules were blocked by P-selectin-specific antibodies and a high-affinity P-selectin ligand 125, 126, 127 .…”

Section: Role Of Enos In Microcirculatory Inflammationmentioning

confidence: 99%

“…Likewise, eNOS knockout mice showed an increased expression of P-selectin 125 . Leukocyte rolling and adhesion in mesenteric venules were blocked by P-selectin-specific antibodies and a high-affinity P-selectin ligand 125, 126, 127 . These observations show possible anti-inflammatory mechanisms of eNOS-derived NO via inhibition of inflammatory processes.…”

Section: Role Of Enos In Microcirculatory Inflammationmentioning

confidence: 99%

Endothelial nitric oxide synthase in the microcirculation

Shu

Keller

Begandt

et al. 2015

Cell. Mol. Life Sci.

105

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Endothelial nitric oxide synthase (eNOS, NOS3) is responsible for producing nitric oxide (NO) - a key molecule that can directly (or indirectly) act as a vasodilator and anti-inflammatory mediator. In this review, we examine the structural effects of regulation of the eNOS enzyme, including post-translational modifications and subcellular localization. After production, NO diffuses to surrounding cells with a variety of effects. We focus on the physiological role of NO and NO-derived molecules, including microvascular effects on vessel tone and immune response. Regulation of eNOS and NO action is complicated; we address endogenous and exogenous mechanisms of NO regulation with a discussion of pharmacological agents used in clinical and laboratory settings and a proposed role for eNOS in circulating red blood cells.

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“…Os dados na literatura quanto ao papel do NO na expressão de L-selectina são escassos e não conclusivos (ROMAN & MCGAHREN, 2006;) e pela primeira vez mostramos que o NO controla a síntese desta molécula.…”

Section: Macrófagos Migrados Para a Cavidade Peritonealunclassified

Inibição in vivo das óxido nítrico sintases: efeitos sobre a expressão de moléculas de adesão e secreção de mediadores inflamatórios

Hebeda¹

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l-NAME–induced neutrophil accumulation in rat lung is not entirely because of interactions with L- and P-selectins or CD18

Cited by 5 publications

References 23 publications

Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature

Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature

Endothelial nitric oxide synthase in the microcirculation

Inibição in vivo das óxido nítrico sintases: efeitos sobre a expressão de moléculas de adesão e secreção de mediadores inflamatórios

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