Monocyte chemoattractant protein-1 and its receptor CCR-2 in piglet lungs exposed to inhaled nitric oxide and hyperoxia. |
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Authors: | I I Ekekezie D W Thibeault R E Garola W E Truog |
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Institution: | Section of Neonatology, Children's Mercy Hospital and Clinic, University of Missouri at Kansas City School of Medicine, Kansas City, Missouri 64108-9883, USA. IEkekezie@cmh.edu |
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Abstract: | Monocyte chemoattractant protein-1 (MCP-1), acting through its C-C chemokine receptor 2 (CCR-2), has important roles in inflammation, angiogenesis, and wound repair. The individual and combined effects of inhaled nitric oxide (NO) and hyperoxia on lung MCP-1 and CCR-2 in relation to lung leukocyte dynamics are unknown. Because MCP-1 gene is up-regulated by oxidants, we hypothesized that inhaled NO with hyperoxia will increase MCP-1 production and CCR-2 expression more than either gas alone. We randomly assigned young piglets to breathe room air (RA), RA+50 ppm NO (RA+NO), O(2), or O(2)+NO for 1 or 5 d before sacrifice. Lungs were lavaged and tissues preserved for hybridization studies, Western blotting, histology, and immunohistochemistry. The results show that lung MCP-1 production and alveolar macrophage count were significantly elevated in the 5-d O(2) and O(2)+NO groups relative to the RA group (p < or = 0.05). In contrast, lung CCR-2 abundance was diminished in the O(2) group (p = 0.05), but not in the O(2)+NO group, compared with the RA group. No difference was detected in any variable studied at 24 h. CCR-2 distribution was similar in all groups with staining of alveolar septa, macrophages, vascular endothelium, and the luminal epithelial surface of airways. We conclude that although hyperoxia increases MCP-1 in young piglet lungs, it also decreases CCR-2 abundance, which may limit participation of MCP-1 in alveolar macrophage recruitment. Inhaled NO, unlike hyperoxia, has no significant independent effect, but its concurrent administration during hyperoxia attenuates the decremental effect of hyperoxia on CCR-2 abundance. |
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