Lung Macrophage Differentiation Antigens in Developing Fetal and Newborn Rat Lungs: A Quantitative Flow Cytometric Analysis with Immunohistochemistry

Abstract.

Relative deficiencies in the number and function of alveolar macrophages (AMs) are present immediately after birth and contribute to increased susceptibility to infection. We used immunohistochemical localization with a panel of monoclonal antibodies to macrophage differentiation markers to characterize lung macrophage antigens relevant to development, and we present here the first study to quantitate these markers using flow cytometric analysis. Rat lung macrophages undergo immunophenotypic maturation seen by a changing number (OX-1, ED-1, ED-2, and ED-9) and distribution (ED-2) of certain lung macrophage differentiation antigens. Quantification of these antibodies revealed that labeling for ED-1 and ED-9 was less on lavageable AMs from early postnatal days than on mature adult AMs. In vitro treatment of adult rat AMs with murine granulocyte-macrophage colony-stimulating factor produces a proliferating population of AMs with a high proliferation index and an immature phenotype, similar to that of newborn AMs. This in vitro model was useful in validating our quantitation of neonatal lung macrophage differentiation antigens. Our quantitative studies of potential markers of AM differentiation in the developing lung may help to focus the study of macrophages in the developing lung on specific cellular and molecular pathways that may control immunologic events during this critical period.