Anti-neutrophil chemokine preserves alveolar development in hyperoxia-exposed newborn rats.
Inflammation may contribute to lung injury and impaired alveolar development in bronchopulmonary dysplasia. We treated hyperoxia-exposed newborn rats with antibodies to the neutrophil chemokine cytokine-induced neutrophil chemoattractant-1 (CINC-1) during 95% O2 exposure to reduce adverse effects of hyperoxia-induced inflammation on lung development. Rats were exposed at birth to air, 95% O2, or 95% O2 + anti-CINC-1 (injected on days 3 and 4). Bromodeoxyuridine (BrdU) was injected 6 h before death. Anti-CINC-1 treatment improved weight gain but not survival at day 8. Anti-CINC-1 reduced bronchoalveolar lavage neutrophils at day 8 to levels equal to air controls. Total detectable lung CINC-1 was reduced to air control levels. Lung compliance was improved by anti-CINC-1, achieving air control levels in the 10-microg anti-CINC-1 group. Anti-CINC-1 preserved proliferating cell nuclear antigen expression in airway epithelium despite 95% O2 exposure. BrdU incorporation was depressed by hyperoxia but preserved by anti-CINC-1 to levels similar to air control. Alveolar volume and surface density were decreased by hyperoxia but preserved by anti-CINC-1 to levels equal to air control. Blockade of neutrophil influx in newborns may avert early lung injury and avoid alveolar developmental arrest that contributes to bronchopulmonary dysplasia.
Auten
R L
RL
Division of Neonatal Medicine, Department of Pediatrics, Neonatal-Perinatal Research Institute, Durham, North Carolina 27710, USA. auten@duke.edu
Mason
S N
SN
Tanaka
D T
DT
Welty-Wolf
K
K
Whorton
M H
MH
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D000906:Antibodies / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002455:Cell Division; D054360:Chemokine CXCL1; D018925:Chemokines / Q000032:analysis; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000276:immunology*; D004247:DNA / Q000378:metabolism; D006133:Growth Substances / Q000276:immunology*; D018496:Hyperoxia / Q000473:pathology / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D051381:Rats; D016019:Survival Analysis; D015430:Weight Gain
D000906:Antibodies; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA; D001973:Bromodeoxyuridine