Effect of carbon dioxide on neonatal mouse lung: a genomic approach

Abstract

Despite the deleterious effects associated with elevated carbon dioxide (CO(2)) or hypercapnia, it has been hypothesized that CO(2) can protect the lung from injury. However, the effects of chronic hypercapnia on the neonatal lung are unknown. Hence, we investigated the effect of chronic hypercapnia on neonatal mouse lung to identify genes that could potentially contribute to hypercapnia-mediated lung protection. Newborn mouse litters were exposed to 8% CO(2), 12% CO(2), or room air for 2 wk. Lungs were excised and analyzed for morphometric alterations. The alveolar walls of CO(2)-exposed mice appeared thinner than those of controls. Analyses of gene expression differences by microarrays revealed that genes from a variety of functional categories were differentially expressed following hypercapnia treatment, including those encoding growth factors, chemokines, cytokines, and endopeptidases. In particular and of major interest, the expression level of genes encoding surfactant proteins A and D, as well as chloride channel calcium-activated 3, were significantly increased, but the expression of WNT1-inducible signaling pathway protein 2 was significantly decreased. The significant changes in gene expression occurred mostly at 8% CO(2), but only a few at 12% CO(2). Our results lead us to conclude that 1) there are a number of gene families that may contribute to hypercapnia-mediated lung protection; 2) the upregulation of surfactant proteins A and D may play a role as anti-inflammatory or antioxidant agents; and 3) the effects of CO(2) seem to depend on the level to which the lung is exposed.

Elevated CO2suppresses specific Drosophila innate immune responses and resistance to bacterial infection

“…To investigate the molecular basis of the physiological effects of hypercapnia and identify CO 2 -responsive promoters to use as markers for dissecting CO 2 -signaling pathways, we performed microarray analysis on adult flies. Similar to the limited changes in gene expression seen in neonatal mice raised in CO 2 (47), exposure of adult flies to 13% CO 2 for 24 h causes fewer than 500 genes to be up-regulated or down-regulated Ͼ1.5-fold, and fewer than 10 by Ͼ10-fold. Importantly, the regulated genes define discrete physiological functions.…”

Morphometry of the epidermis of an invasive megascoelecid earthworm (Amynthas gracilis, Kinberg 1867) inhabiting actively volcanic soils in the Azores archipelago

“…The high soil temperature at Furnas also presumably increases metabolic O 2 consumption and demand, adding a premium to improved trans-epidermal diffusion efficiency. The structural change in the gas permeable exchange surface of Amynthas seems to be functionally analogous to the thinning of alveolar epithelia observed in CO 2 -exposed neonatal mice compared with controls (Li et al, 2006).…”

Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α

“…We have previously shown that chronic inhalation of CO 2 prevented PHT in chronic hypoxia-exposed neonatal rats (31), a model in which pulmonary inflammation is not apparent (47). Given the major putative role for lung inflammation in the pathogenesis of BPD (61,62,66) and evidence for anti-inflammatory effects of inhaled CO 2 (37,40,45,72), we were interested in examining the effects of therapeutic hypercapnia on an alternative rat model in which inflammation is a prominent early feature. The concentrations of CO 2 examined in bleomycin-exposed animals were intended to reproduce what are generally considered, in the clinical setting, to represent moderate (5% CO 2 ; mean elevation of Pa CO 2 15-20 mmHg) and severe (7% CO 2 ; mean elevation of Pa CO 2 35 mmHg) levels of hypercapnia.…”