High CO2 Levels Impair Lung Wound Healing.

High CO2 Levels Impair Lung Wound Healing. Am J Respir Cell Mol Biol. 2020 Apr 10;: Authors: Bharat A, Angulo M, Sun H, Akbarpour M, Alberro A, Cheng Y, Shigemura M, Berdnikov S, Welch LC, Kanter JA, Budinger GRS, Lecuona E, Sznajder JI Abstract Delayed lung repair leads to alveolo-pleural fistulae which are a major cause of morbidity following lung resections. We have reported that intrapleural hypercapnia is associated with delayed lung repair after lung resection. Here, we provide new evidence that hypercapnia delays wound closure of both large airway and alveolar epithelial cell monolayers due to inhibition of epithelial cell migration. Cell migration and airway epithelial wound closure was dependent on Rac1-GTPase activation which was suppressed by hypercapnia directly, through the upregulation of AMP-kinase, and indirectly, through inhibition of injury-induced NFkB-mediated CXCL12 release, respectively. Both these pathways were independently suppressed since dominant negative AMP-kinase rescued the effects of hypercapnia on Rac1-GTPase in uninjured resting cells while proteasomal inhibition reversed the NFkB-mediated CXCL12 release during injury. Constitutive over-expression of Rac1-GTPase rescued the effects of hypercapnia on both pathways as well as on wound healing. Similarly, exogenous recombinant CXCL12 reversed the effects of hypercapnia through Rac1-GTPase activation by its receptor CXCR4. Moreover, CXCL12 transgenic mur...
Source: Respiratory Care - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research