Age-dependent changes in porcine alveolar macrophage function during the postnatal period of alveolarization

Abstract

During early postnatal ontogeny in most mammals, the lung is structurally and functionally immature. In some species with relatively altricial lung morphology, there is evidence of a coupling between functional maturity of the pulmonary cellular immune system and alveolar maturation. Herein, we examine changes in alveolar macrophage (AM) number and function occurring during alveolarization in a more precocial species, the pig, to determine if heightened oxidative metabolism and phagocytic ability is similarly delayed until completion of lung morphogenesis. We assessed cell differential in lavage fluid and evaluated two main functional parameters of AM phagocytic response, the generation of reactive oxygen species (ROS), and particle internalization. AM functional maturation occurred mainly during the first postnatal week: the proportion of AMs, ROS generation, and phagocytosis all increased significantly. These results suggest maturational improvement of the impaired AM-based pulmonary immune system of the neonate piglet occurs during the postnatal period of rapid alveolarization.

CD11b+Mononuclear Cells Mitigate Hyperoxia-Induced Lung Injury in Neonatal Mice

“…To this end, IL-10-expressing, alternately activated M2 macrophages are present in the placenta (11,44). Consistent with published reports (41,45), neonatal lung leukocytes evolved in the early postnatal period. Specifically, alveolar macrophages were not present until a few days after birth.…”

M2 macrophage polarisation is associated with alveolar formation during postnatal lung development

“…Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling in fetal macrophages upregulates pro-inflammatory mediators such as interleukin-1β and alters expression of Wnt7b, bone morphogenic protein-4 [23] and fibroblast growth factor-10 [52]. Given the correlation between the timing of lung structural establishment and lung immunological maturity [53], it is plausible that the developmental deficits associated with inflammation may also result from skewing of macrophages prematurely away from their organogenic activities toward pro-inflammatory mediation roles.…”

Pre‐ and Postnatal Lung Development: An Updated Species Comparison

“…Adherence, intracellular production, and extracellular release of oxygen radical species and phagocytic capacities of AM were deficient in rats up to 6 weeks of age (Delacourt et al, , Goldman et al, ). Rat AMs attained full oxidant releasing capacity only when the major period of postnatal alveolar morphogenesis was completed and, it is hypothesized, the lung tissue was more resistant to oxidant stress (Dickie et al, ). In contrast, the chemotactic properties of AMs seem to develop somehow earlier, as described by Coonrod et al (), where granulocyte concentrations in lung tissue after experimental microbe infection reached adult values as early as PND 7.…”

“…In pig BALF, the proportion of AMs increased from 60 to 70% at PND 2 to more than 90% at PND 7, while cell numbers of polymorphonuclear neutrophils and lymphocytes decreased from > 30% at PND 2 to < 10% at PND 7. The proportion of cells reactive to nitroblue tetrazolium increased from ∼40% at PND 2 to ∼60% at PND 7 (Dickie et al, ). In the guinea pig, a greater oxidant generation in the AMs of young juveniles (∼PND 10) is seen compared with adults and it may help compensate for their lower serum opsonic activity (Kato et al, ).…”