Prevention of pulmonary alveolar macrophage proliferation in newborn rabbits by hyperoxia

As a test of the hypothesis that hyperoxia might hinder the growth of nascent lung macrophages, term newborn rabbits were treated with room air or increasing oxygen concentrations (40%, 80%, or greater than or equal to 95%) for 96 hours after birth. After 24, 48, 72, and 96 hours of environmental exposure, pulmonary alveolar macrophage population kinetics were determined by three methods: (1) bronchoalveolar lavage cell yields, (2) thymidine incorporation by macrophages, and (3) assessment of macrophage cell division by mitotic indices. Newborn rabbits kept in room air or 40% inspired O2 showed a steady increase of macrophages in lung lavage, but pups treated with 80% or greater than or equal to 95% oxygen showed no rise of macrophage yield in lung washings after 96 hours of exposure (P less than 0.02). The diminished macrophage yield noted in pups treated with 80% or greater than or equal to 95% oxygen was explained by rates of thymidine uptake and macrophages replication (mitotic indices) that were greater than 12-fold lower than values seen in rabbit pups housed in room air or 40% inspired O2 for 96 hours (P less than 0.05). These findings could not be attributed to malnutrition caused by oxygen toxicity because all groups appeared well and gained weight equally during the period of exposure. We conclude that acute hyperoxia impedes the intraalveolar proliferation of lung macrophages, an observation that may have implications regarding host defense and for repair and growth of the lung in neonates needing respiratory support.