FUNCTIONAL IMMATURITY OF RAT ALVEOLAR MACROPHAGES DURING POSTNATAL-DEVELOPMENT

Alveolar macrophages (AM) are important in the regulation of immune re sponses in the lung, through their role as scavenger cells and through the production of many bioactive factors. Because in early infancy pu lmonary infections are a recurrent problem, we studied the postnatal f unctional maturation of AM in a rat model. AM were isolated from rat l ungs by bronchoalveolar lavage at several time intervals after birth a nd tested for their ability to ingest Escherichia coli in the presence of surfactant protein A (SP-A). Furthermore, their capacity to produc e nitric oxide (NO) and interleukin-1 beta (IL-1 beta) after in vitro lipopolysaccharide (LPS) stimulation was analysed, as well as their ca pacity to downregulate proliferation of T cells from both mature and n eonatal rats. SP-A-mediated phagocytosis of E. coli by AM was reduced in 14-day-old neonatal rats, as compared with mature rats (P less than or equal to 0.05). Also the IL-1 beta production by rat AM after LPS stimulation was impaired at 14 days of age, as compared with IL-1 beta production by AM from mature rats (P less than or equal to 0.05). In contrast, the LPS-induced NO production by rat AM as well as the capac ity to inhibit T-cell proliferation were well developed at all ages te sted. In conclusion, during postnatal development the rat AM is functi onally immature, with respect to phagocytosis and secretion of inflamm atory mediators. These differences may underly the enhanced susceptibi lity to pulmonary infections as found in human neonates.