Effect of CO₂on LPS-induced cytokine responses in rat alveolar macrophages

Abstract

veolar macrophages (AM) may be exposed to a range of CO 2 and pH levels depending on their location in the alveoli and the health of the lung. Cytokines produced by AM contribute to inflammation in acute lung injury (ALI). Current ventilatory practices for the management of ALI favor low tidal volumes, which can give rise to increases in CO2 and changes in pH of the alveolar microenvironment. Here we examined the effect of CO2 on cytokine release from LPS-stimulated rat AM. AM were incubated for 1-4 h under different atmospheric gas mixtures ranging from 2.5-20% CO2. To distinguish between effects of pH and CO 2, the culture media were also buffered to pH 7.2 with NaHCO 3. Cell metabolic activity, but not cell viability, decreased and increased significantly after 4 h at 20 and 2.5% CO 2, respectively. Increasing CO 2 decreased TNF-␣ secretion but had no effect on lysate TNF-␣. Buffering the media abated the effects of CO 2 on TNF-␣ secretion. CO 2 increased cytokine-induced neutrophil chemoattractant factor-1 secretion only when the pH was buffered to 7.2. Effects of CO2 on cytokine responses were reversible. In conclusion, the effects of CO 2 on cytokine lysate levels and/or secretion in AM are cytokine specific and, depending on both the cytokine and the immediate

Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages

“…In contrast, MMP-9 production stimulated by LPS was suppressed by SMS 201-995 in rat macrophage Kupffer cells [12]. In particular, the fact that 24 h incubation with CH-275 or L-779,976 induced a marked decrease in macrophage viability, as assessed by MTT assay (an index of the metabolic activity of cells), without affecting the secretion of proMMP-9, suggests that proMMP-9 secretion is immediate and rapid after LPS activation, in agreement with previous results reporting the secretion of different cytokines in rat alveolar macrophages [77]. Conversely, the effects of different stimuli on the metabolic activity of macrophages and the secretion of proinflammatory mediators are clearly not superimposable [78,79].…”

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

“…CO 2 reacts with water to form carbonic acid (H 2 CO 3 ) and previous investigations of hypercapnic innate immune suppression in mammalian immune cells have implicated-but not proven-acidosis as the critical mediator (9,11,62). Here, we show that elevated CO 2 levels can suppress immune responses in S2* cells independent of extracellular pH effects.…”

“…In vitro and animal studies have shown that hypercapnia can suppress mammalian inflammatory responses (6)(7)(8), including NF-B-regulated cytokine production (9)(10)(11), which could contribute to the poor outcomes of patients with COPD and CF who frequently suffer from both hypercapnia and bacterial lung infections (12,13). Hypercapnic immune suppression may be evolutionarily conserved because hypercapnia, in combination with hypoxia, also suppresses innate immune responses in shrimp, oysters, and crabs (14)(15)(16).…”

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

“…That both macrophage numbers and TNF-␣ expression/content were found to be attenuated by concurrent exposure to 7% CO 2 suggested a causative role in PHT, with a lesser effect of 5% CO 2 and colocalization indicating that macrophages were the major source of TNF-␣. Lang et al (39) have described inhibition of TNF-␣ secretion by CO 2 in pulmonary macrophages activated by LPS in vitro. Exogenous administration of TNF-␣ is also known to increase pulmonary vascular reactivity in isolated rat lungs (68), and its overexpression has been described to cause emphysematous lung structure and PHT in mice (16,17), similar to bleomycininduced lung injury.…”