INCREASED 92-KD GELATINASE ACTIVITY FROM ALVEOLAR MACROPHAGES IN NEWBORN RATS

The functional immaturity of neonatal alveolar macrophages (AM) may co ntribute to the increased susceptibility of neonates to lung injury. B ecause the secretion of proteinases by neonatal AMs may be involved in normal postnatal lung development and in repair after lung injury, we evaluated the capacity of neonatal AMs to secrete 92 kD Type IV colla genase. AMs were obtained by bronchoalveolar lavage from newborn rats at different postnatal ages. Total gelatinase activity was measured by zymography in AM-conditioned media. Spontaneous secretion of gelatina se from AMs varied significantly with age, the highest levels being fo und immediately after birth. Stimulation of AMs by PMA induced a four- to fivefold greater increase in total gelatinase activity during the first 10 d of postnatal life compared with adulthood. Using [H-3]gelat in as the substrate, we found high free gelatinase activity only withi n 24 h after birth; data obtained after exposing cells to natural surf actant suggested that surfactant may account in part for this increase in free gelatinase activity. No secretion of tissue inhibitor of meta lloproteinases (TIMP) by AMs was detectable in newborns within 24 h af ter birth. We conclude that AMs from newborn rats are able to secrete more gelatinase than AMs from adults, and this enzyme production profi le during the neonatal period may contribute to the fact that newborns with lung injury are at high risk for extracellular matrix degradatio n.