Functional immaturity of rat alveolar macrophages during postnatal development.
Alveolar macrophages (AM) are important in the regulation of immune responses in the lung, through their role as scavenger cells and through the production of many bioactive factors. Because in early infancy pulmonary infections are a recurrent problem, we studied the postnatal functional maturation of AM in a rat model. AM were isolated from rat lungs by bronchoalveolar lavage at several time intervals after birth and tested for their ability to ingest Escherichia coli in the presence of surfactant protein A (SP-A). Furthermore, their capacity to produce nitric oxide (NO) and interleukin-1 beta (IL-1 beta) after in vitro lipopolysaccharide (LPS) stimulation was analysed, as well as their capacity to downregulate proliferation of T cells from both mature and neonatal rats. SP-A-mediated phagocytosis of E. coli by AM was reduced in 14-day-old neonatal rats, as compared with mature rats (P < or = 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 < or = 0.05). In contrast, the LPS-induced NO production by rat AM as well as the capacity to inhibit T-cell proliferation were well developed at all ages tested. In conclusion, during postnatal development the rat AM is functionally immature, with respect to phagocytosis and secretion of inflammatory mediators. These differences may underly the enhanced susceptibility to pulmonary infections as found in human neonates.
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
J M
JM
Bakker
E
E
Broug-Holub
H
H
Kroes
E P
EP
van Rees
G
G
Kraal
J F
JF
van Iwaarden
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D002478:Cells, Cultured; D003208:Concanavalin A; D004926:Escherichia coli; D005260:Female; D007375:Interleukin-1 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D010587:Phagocytosis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D003208:Concanavalin A; D009569:Nitric Oxide