Abstract
Summary: Neonatal guinea pig pulmonary response to oxygen exposure Fio2 > 0.9 resulted in an increase in total cell number in lung lavage. Alveolar macrophages initially increased within 48 h of exposure. Polymorphonuclear leukocytes and macrophages exceeded age-matched neonatal control values by 72 h of oxygen exposure. By 144 h of life, total inflammatory cell number still exceeded control cell populations. Chemotaxis of alveolar macrophages to N-formyl-methionyl-phenylalanine (1 × 10−5 M) exceeded chemotaxis of air-exposed controls. Although initially depressed, by 72 h of Fio2 > 0.9 polymorphonuclear leukocyte chemotaxis increased 6-fold. Endogenous chemotactic peptides were demonstrated in lung lavage supernatant of oxygen-exposed neonatal guinea pigs. Elastase activity rose in oxygen exposed guinea pigs by 72 h of life. Lung lavage disaturated phosphatidyl-choline in oxygen-exposed neonates exceeded control values 4-fold. In a preliminary study, lung effluent elastase activity was found to be increased in human neonates with respiratory distress syndrome over the first days of life compared to infants intubated but without lung disease. In infants developing bronchopulmonary dysplasia, tracheal aspirate protease activity remained greater than 10−3 U for over 10 days and up to 5 weeks of age.
Speculation: Lung damage in neonatal guinea pigs from elevated oxygen exposure results in lung cell injury with enhanced chemotaxis for polymorphonuclear leukocytes and macrophages. These cells release proteolytic enzymes into pulmonary effluent. These proteolytic enzymes may, if unabated, result in lung connective tissue damage. Although previously described only in adult animals and implicated in the adult respiratory distress syndrome, similar processes may be operative in the development of neonatal bronchopulmonary dysplasia.
It is tempting to extrapolate our finding of higher amounts of elastase activity in tracheal effluent in infants developing bronchopulmonary dysplasia compared to other infants without lung disease or respiratory distress syndrome to similar findings in neonatal guinea pigs exposed to high concentrations of oxygen. Although this extrapolation may not be justified without further studies documenting the precise source of elastase activity, monitoring of lung effluent protease activity may provide useful biochemical indices of neonatal lung injury. Modulation and/or prevention of neonatal lung injury may be possible by reducing proteolytic activity either by reducing lung inflammation or increasing endogenous antiprotease activity.
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Allen Merritt, T. Oxygen Exposure in the Newborn Guinea Pig Lung Lavage Cell Populations, Chemotactic and Elastase Response: a Possible Relationship to Neonatal Bronchopulmonary Dysplasia. Pediatr Res 16, 798–805 (1982). https://doi.org/10.1203/00006450-198209000-00018
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DOI: https://doi.org/10.1203/00006450-198209000-00018
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