title: Lung inflammation in hyperoxia can be prevented by antichemokine treatment in newborn rats.
abstract: Hyperoxia may contribute to lung disease in newborns through effects on alveolar neutrophils which predominate in respiratory distress syndrome and other acute lung injuries. Neutrophil chemokines such as interleukin-8 (IL-8) regulate chemoattraction, and are elevated in tracheal aspirates of newborns who develop bronchopulmonary dysplasia (BPD). Blockade of neutrophil chemokines may reduce hyperoxia-induced inflammatory lung injury and BPD. We therefore tested the hypothesis that hyperoxia contributes to elevations of rat neutrophil chemokines, cytokine-induced neutrophil chemoattractant-1 (CINC-1), and macrophage inflammatory protein-2 (MIP-2) in newborn rat lung. Newborn rats were exposed to air or 95% O(2) for 8 d. CINC-1 and MIP-2 were measured in whole lung homogenates by ELISA. Newborn 95% O(2)-exposed animals were given anti-CINC-1 or anti-MIP-2, 1, 5, or 10 microg on Days 3 and 4 of 95% O(2) exposure. Bronchoalveolar lavage (BAL) was performed after perfusion on day 6 to evaluate airway neutrophils, and myeloperoxidase (MPO) was measured in perfused whole lung. Lungs were examined histologically and immunohistochemically for effects of 95% O(2) +/- antichemokine. CINC-1 and MIP-2 increased nearly tenfold by Day 8 95% O(2) treatment versus air control. CINC-1 and MIP-2 immunolabeling was increased in alveolar macrophages and alveolar epithelium in 95% O(2). Anti-CINC-1 and anti-MIP-2 treatment at every dose reduced neutrophil number > 90% in BAL. Anti-CINC-1 10 microg reduced tissue MPO by 50%. Antichemokine treatment on days 3 and 4 prevented alveolar septal thickening and reduced chemokine immunolabeling on Day 6. Hyperoxia-induced neutrophil influx is mediated in part by CINC-1 and MIP-2 in newborn rats and can be partially prevented by treatment with anti-CINC-1 and anti-MIP-2.
authors: Neonatal Perinatal Research Institute, Division of Neonatal Medicine, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors: H
authors: H
authors: Deng
authors: S N
authors: SN
authors: Mason
authors: R L
authors: RL
authors: Auten
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007150:Immunohistochemistry; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D015846:Monokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D013997:Time Factors
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D015846:Monokines