Hyperoxia potentiates Ureaplasma urealyticum pneumonia in newborn mice

Abstract

The effect of continuous exposure to 80% oxygen on newborn mice with Ureaplasma urealyticum pneumonia was determined. Mice were inoculated intranasally with either U. urealyticum or sterile broth and then housed in either 80% oxygen or room air (21% oxygen). The mice were sacrificed at either 7 or 14 days after inoculation. Significantly more mice in the U. urealyticum group housed in 80% 02 than in the room airexposed group were culture positive 14 days after inoculation (P = 0.042), but no difference was found at 7 days. The presence of alveolar macrophages, neutrophils, and lymphocytes and alveolar wall thickness were determined. Overall, the group housed in 80% 02 and inoculated with U. urealyticum had severe pulmonary lesions at both time points, while the lesion severity in the room air-exposed group inoculated with U. urealyticum and the group housed in 80% 02 and inoculated with sterile broth was dependent on the time point. Mortality was significantly higher in the group housed in 80% 02 and inoculated with U. urealyticum than it was in all other groups (P < 0.001). Our results indicate that hyperoxia causes the persistence of U. urealyticum in the lungs of newborn mice, acutely potentiates the inflammatory response, and turns an otherwise selflimited pneumonia into a lethal disease.

Infection with Ureaplasma urealyticum and Mycoplasma hominis and the development of chronic lung disease in preterm infants

“…There are many triggers to inflammation within the lung, and U. urealyticum has been shown both in vitro and in animal models to be capable of stimulating such an inflammatory response (15,16). This is more marked in immature animals and is exacerbated by oxygen (12,17). However, it is possible that the development of CLD encourages persistence of the genital mycoplasmas in the lung and that, although associated, there is no direct cause and effect.…”

Graphene-based sensing of oxygen transport through pulmonary membranes

“…It is noteworthy that membrane misalignment across the air/water interface in the alveoli and increased stalk formation caused by the presence cardiolipin and Ca 2þ are both expected to induce significant oxygen permeation imbalance. Irregularities in O 2 and CO 2 gas transport and exchange might lead to abnormalities in blood gas composition which is a factor implicated in lung diseases 14,15 . It could be argued that phase separation in the lung membranes could be implicated in oxygen permeability.…”

“…The formation of membrane stalks leads to enhanced oxygen gas permeability through the hydrophobic hemifusion points. Respiratory pathologies often cause edema and fluid flow imbalance in the alveoli and an interruption of oxygen flow should be expected, however, abnormally accelerated oxygen gas transport (hyperoxia) has been observed in mammalian lungs in diseased states, in particular during pneumonia 14,15 . We conjecture that this is consistent with a defective lung membrane with an increased number of stalk defects.…”

“…It has been established that increased oxygen supply in the lungs (hyperoxia) is a pathological factor in bacterial pneumonia. This has been observed in newborn mice where hyperoxia potentiates bacterial growth and inflammatory responses 14 , as well as being an important co-factor for the development of acute lung injury and lethality in L. pneumophila pneumonia 15 . In addition, lung fluid from humans and mice infected with bacterial pneumonia displays significantly elevated contents of cardiolipin, a mitochondrial-specific phospholipid 16 .…”

Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns.

“…U. urealyticum can induce ciliostasis and mucosal lesions in human fetal tracheal organ cultures (96). Furthermore, ureaplasmas isolated from the lungs of human infants with congenital pneumonia produce pneumonia in newborn animals (24,112,151).…”