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

The functional immaturity of neonatal alveolar macrophages (AM) may contribute to the increased susceptibility of neonates to lung injury. Because 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 collagenase. 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 gelatinase from AMs varied significantly with age, the highest levels being found 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]gelatin as the substrate, we found high free gelatinase activity only within 24 h after birth; data obtained after exposing cells to natural surfactant suggested that surfactant may account in part for this increase in free gelatinase activity. No secretion of tissue inhibitor of metalloproteinases (TIMP) by AMs was detectable in newborns within 24 h after birth. We conclude that AMs from newborn rats are able to secrete more gelatinase than AMs from adults, and this enzyme production profile during the neonatal period may contribute to the fact that newborns with lung injury are at high risk for extracellular matrix degradation.