Sublethal endotoxemia promotes pulmonary cytokine-induced neutrophil chemoattractant expression and neutrophil recruitment but not overt lung injury in neonatal rats.
Gram-negative sepsis and septic shock remain major causes of morbidity and mortality in the newborn. Respiratory failure is a common feature in neonatal sepsis regardless of the presence or absence of associated pneumonia. In adult animal models, cytokine-induced neutrophil chemoattractant (CINC) is a potent chemoattractant for neutrophils and believed to play a role in endotoxin-induced lung injury. We examined this in a neonatal model. Ten-day-old Sprague-Dawley rats were injected with Salmonella enteritidis endotoxin (ETX) 0.03 mg/kg i.p. and sacrificed at baseline, 30 min, 1, 2, 4, 8 and 16 h post-ETX. Blood was collected by cardiac puncture. After bronchoalveolar lavage, lung tissue was collected and evaluated for neutrophil (polymorphonuclear leukocyte) recruitment by myeloperoxidase assay (MPO). Lung CINC expression was measured by Northern blot and ELISA. Peripheral blood leukocytosis was noted at 1 h (p < 0.001) with counts below baseline at 2 and 4 h. Differential counts revealed neutrophilia at 8 h (p < 0.001). MPO revealed pulmonary PMN recruitment peaking at 1 h (p < 0.05) and CINC RNA and protein expression peaked slightly later at 2 h (p < 0. 001). No overt lung injury was noted by bronchoalveolar lavage cell counts or by histology. Therefore, pulmonary CINC expression and neutrophil recruitment follows LPS exposure in neonatal rats. This may represent priming of the lung tissue and a secondary event may be necessary for injury to occur.
Tillema
M S
MS
Ronald McDonald Children's Hospital and Burn Shock Trauma Institute, Loyola University Medical Center, Maywood, IL 60153, USA. mtillem@luc.edu
Lorenz
K L
KL
Weiss
M G
MG
Dries
D J
DJ
D000818:Animals; D015152:Blotting, Northern; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000032:analysis / Q000235:genetics*; D019446:Endotoxemia / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006133:Growth Substances / Q000032:analysis / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D007958:Leukocyte Count; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology; D009504:Neutrophils / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012477:Salmonella enteritidis
D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D009195:Peroxidase