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), O2, or O2+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 O2 and O2+NO groups relative to the RA group (p ≤ 0.05). In contrast, lung CCR-2 abundance was diminished in the O2 group (p ≤ 0.05), but not in the O2+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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Abbreviations
- MCP-1:
-
monocyte chemoattractant protein-1
- NO:
-
nitric oxide
- MPO:
-
myeloperoxidase
- CCR-2:
-
C-C chemokine receptor 2
- RA:
-
room air
- RPA:
-
ribonuclease protection assay
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The authors thank Mary S. Bailey for her administrative assistance and patience in preparation of this manuscript.
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Supported in part by NIH R-01 HL62079 and by a Physician Scientist Award from Children's Mercy Hospitals and Clinics (W.E.T.) and Katherine B. Richardson Foundation (I.I.E. and D.W.T.).
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Ekekezie, I., Thibeault, D., Garola, R. et al. Monocyte Chemoattractant Protein-1 and Its Receptor CCR-2 in Piglet Lungs Exposed to Inhaled Nitric Oxide and Hyperoxia. Pediatr Res 50, 633–640 (2001). https://doi.org/10.1203/00006450-200111000-00017
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DOI: https://doi.org/10.1203/00006450-200111000-00017
