Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung.
Macrophage-derived cytokines may provoke the inflammatory response in lung injury. Because macrophage influx is a prominent feature of the cellular inflammatory response accompanying the development of bronchopulmonary dysplasia, we hypothesized that blocking macrophage influx would reduce overall cellular influx and oxidative damage. Newborn rats were exposed at birth to 95% O(2) or air for 1 wk, and hyperoxia-exposed pups were injected with anti-monocyte chemoattractant protein-1 (MCP-1) or IgG control on days 3-5. MCP-1 was increased in bronchoalveolar lavage fluid and in histological sections from the 95% O(2)-exposed, IgG-injected pups compared with air-exposed controls. At 1 wk, anti-MCP-1-treated pups had reduced leukocyte numbers, both macrophages and neutrophils, in bronchoalveolar lavage fluid compared with IgG-treated controls. Cytokine-induced neutrophil chemoattractant-1, the rat analog of IL-8, was not significantly decreased in lavage fluid but was reduced in lung cells in anti-MCP-1-treated pups. Tissue carbonyls, a measure of protein oxidation, were decreased in anti-MCP-1-treated pups. Anti-MCP-1 treatment prevented neutrophil influx and reduced protein oxidation in hyperoxia-exposed newborn rats.
Vozzelli
Michael A
MA
Department of Pediatrics, Division of Neonatal Medicine, Neonatal-Perinatal Research Institute, Durham, NC 27710, USA. auten@duke.edu
Mason
S Nicholas
SN
Whorton
Mary H
MH
Auten
Richard L
RL
D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D001997:Bronchopulmonary Dysplasia / Q000276:immunology*; D002244:Carbon / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology; D019743:Chemokines, CXC / Q000378:metabolism; D005260:Female; D006801:Humans; D018496:Hyperoxia / Q000276:immunology; D000860:Hypoxia / Q000276:immunology*; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D018384:Oxidative Stress / Q000276:immunology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018932:Chemokine CCL2; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D002244:Carbon