Increased Intrapulmonary Retention of Radiolabeled Neutrophils in Early Oxygen Toxicity

Rinaldo, Jean E.; English, D.; Levine, Joel S.; Stiller, Robert L.; Henson, Jan E.

doi:10.1164/ajrccm/137.2.345

Cited by 40 publications

(16 citation statements)

References 8 publications

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“…This was consistent with findings from other laboratories in which increases in the numbers of radiolabeled neutrophils were detected during hyperoxic lung injury (20). To determine if there was a temporal association between the appearance of neutrophils in the bronchoalveolar lavage fluid and the expression of mRNA for the adhesion molecules, ICAM-1, Eselectin, VCAM-1, or P-selectin, we exposed rats to an atmosphere of >95% oxygen for up to 72 hr.…”

Section: Rna Extaction and Northern Blot Analysissupporting

confidence: 87%

Attenuation of oxidant-induced lung injury by 21-aminosteroids (lazaroids): correlation with the mRNA expression for E-selectin, P-selectin, ICAM-1, and VCAM-1.

Griffin¹,

Krzesicki²,

Fidler³

et al. 1994

Environ Health Perspect

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We compared the effects of treatment with methylprednisolone or the 21-aminosteroids, U-74389 and U-74006F (Tirilizad mesylate), on hyperoxic lung injury and the associated expression of mRNA for several adhesion molecules in rats. Inhalation of >95% oxygen for up to 72 hr in Sprague-Dawley rats produced a marked increase in lung weight and an accumulation of fluid in the thorax when compared with air-breathing controls. Hyperoxia also induced a marked neutrophil-rich influx of inflammatory cells into the bronchial lumen as measured by bronchoalveolar lavage. Neutrophil numbers in bronchoalveolar lavage fluid peaked after 60 hr of exposure to > 95% oxygen; this was associated with a marked upregulation of mRNA for the adhesion molecules P-selectin and E-selectin but not VCAM-1. mRNA for ICAM-1 was constitutively expressed at high levels in both air-breathing controls and in the lungs of rats exposed to high concentrations of oxygen. Pretreatment with the 21-aminosteroids reduced hyperoxic lung damage and improved survival times in animals exposed to >95% oxygen. However, treatment with methylprednisolone significantly decreased survival times. Treatment with U-74389 did not significantly (p > 0.05) inhibit the BAL neutrophilia and did not significantly (p > 0.05) reduce hyperoxia-induced increases in mRNA expression for P-selectin and E-selectin. The inhibition of hyperoxic lung damage coupled with improved survival seen in treated animals suggests that 21-aminosteroids may provide valuable treatments for pulmonary disorders in which oxidant damage has been implicated. -Environ Health Perspect 102 (Suppl 10):193-200 (1994)

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Section: Rna Extaction and Northern Blot Analysissupporting

confidence: 87%

Attenuation of oxidant-induced lung injury by 21-aminosteroids (lazaroids): correlation with the mRNA expression for E-selectin, P-selectin, ICAM-1, and VCAM-1.

Griffin¹,

Krzesicki²,

Fidler³

et al. 1994

Environ Health Perspect

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“…lung injury in hyperoxia [4,5], there is also data to suggest that hyperoxic lung injury may occur in the absence of neutrophils, as shown in a previous study, where neutrophil depletion by cyclophosphamide did not affect lung oedema in rats exposed to hyperoxia [23]. The production of free radicals has been shown to contribute significantly to hyperoxia-induced lung injury, and a number of studies have shown an improvement in survival with the use of free radical scavengers.…”

Section: Discussionmentioning

confidence: 89%

“…In adult rats, lung injury becomes evident after 50 h, and death usually occurs within 72 h of exposure to 100% oxygen [1]. Neutrophils accumulate in the lungs of rats soon after exposure to 100% oxygen, and may play a role in this form of acute lung injury [4,5].…”

mentioning

confidence: 99%

Pentoxifylline does not protect against hyperoxic lung injury in rats

Naureckas¹,

Benjaminov²,

Hoffer³

et al. 1994

Eur Respir J

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P Pe en nt to ox xi if fy yl ll li in ne e d do oe es s n no ot t p pr ro ot te ec ct t a ag ga ai in ns st th hy yp pe er ro ox xi ic c l lu un ng g i in nj ju ur ry y i in n r ra at ts s The drug pentoxifylline has been shown to have a protective effect in other models of lung injury. We sought to determine whether pentoxifylline protects against hyperoxic lung injury in rats by decreasing the accumulation of neutrophils within the lung. A total of 84 rats were studied. Twenty four rats were randomized into four groups. Two groups of rats were pretreated for 48 h with either pentoxifylline (20 mg·kg -1 ) or saline, and then exposed to >95% O 2 for 60 h while treatments continued. Two groups of control rats received the same treatment regimens as the O 2 -exposed animals, but breathed room air. Neutrophil accumulation in the lung was quantified both by histology and myeloperoxidase activity.Lung neutrophil accumulation increased in the oxygen-exposed group receiving pentoxifylline as compared to oxygen-or air-exposed rats receiving saline injections. Total glutathione was higher in lung homogenates from the hyperoxic, pentoxifylline-treated group than in homogenates from the other three groups. To study survival, 60 rats were exposed to >95% O 2 for 120 h, 30 rats were pretreated with pentoxifylline, and 30 received saline. Survival after 120 h of exposure to hyperoxia was not altered by pentoxifylline treatment (pentoxifylline treated: 6 out of 30 survived; saline treated: 2 out of 30 survived).We conclude that pentoxifylline does not reduce mortality or lung injury in rats exposed to hyperoxia and is associated with an increase in lung neutrophil accumulation.

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“…The migration of neutrophils into the lung, within the 1st week of the start of exposure to high oxygen, reflects an early response to oxidant stress (Rinaldo et al 1988). As exposure continues this diminishes, and PAMs (which also increase early) are found in increasing numbers (Horinouchi et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Expression of nitric oxide synthase isoforms (NOS II and NOS III) in adult rat lung in hyperoxic pulmonary hypertension

Steudel

Watanabe

Dikranian

et al. 1999

Cell and Tissue Research

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Breathing air with a high oxygen tension induces an inflammatory response and injures the microvessels of the lung. The resulting development of smooth muscle cells in these segments contributes to changes in vasoreactivity and increased pulmonary artery pressure. This in vivo study determines the temporal and spatial expression of endogenous endothelial nitric oxide synthase (NOS III) and inducible NOS (NOS II), important enzymes regulating vasoreactivity and inflammation, in the adult rat lung during the development of experimental pulmonary hypertension induced by oxidant injury. We analyzed the cellular distribution of these NOS isoforms, using specific antibodies, and assessed enzyme activity at baseline and after 1-28 days of hyperoxia (FIO2 0.87). The number of NOS III-immuno-positive endothelial cells increased early in hyperoxia and then remained high. By day 28, the relative number of these cells had increased from 40% in proximal vessels and 13-16% in distal alveolar vessels of the normal lung to 73-86% and 40-59%, respectively, in hyperoxia. Pulmonary alveolar macrophages (PAMs), normally few in number and only weakly immunopositive for NOS II or III in the normal lung, increased in number in hyperoxia and were strongly immunopositive for each isoform. These morphological data were supported by a temporal increase in total and calcium-independent NOS activity. Thus NOS expression and activity significantly increased in hyperoxia as pulmonary hypertension developed, and NOS III expression increased selectively in vascular endothelial cells, while both NOS isoforms were expressed by the PAM population. We conclude that this increase in expression of a potent vasodilator, an antiproliferative agent for smooth muscle cells, and an antioxidant molecule represents an adaptive response to protect the lung from oxidant-induced vascular and epithelial injury.

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Increased Intrapulmonary Retention of Radiolabeled Neutrophils in Early Oxygen Toxicity

Cited by 40 publications

References 8 publications

Attenuation of oxidant-induced lung injury by 21-aminosteroids (lazaroids): correlation with the mRNA expression for E-selectin, P-selectin, ICAM-1, and VCAM-1.

Attenuation of oxidant-induced lung injury by 21-aminosteroids (lazaroids): correlation with the mRNA expression for E-selectin, P-selectin, ICAM-1, and VCAM-1.

Pentoxifylline does not protect against hyperoxic lung injury in rats

Expression of nitric oxide synthase isoforms (NOS II and NOS III) in adult rat lung in hyperoxic pulmonary hypertension

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