The kinetics and distribution of different macrophage populations in the developing rat skin

Macrophages play important roles in host defense and homeostasis. In contrast to adulthood, far less is known about macrophage populations in fetuses and neonates. Macrophages were evaluated in the developing rat skin at different anatomical sites (head, anterior dorsal, posterior dorsal, and abdomen) of F344 rats obtained on gestational days 18 and 20, on neonatal days 1-21, and at adult weeks 5-15. The numbers of macrophages in the epidermis, dermis or perifollicular areas that were positive for ED1 (exudative macrophages with activated phagocytosis), ED2 (resident macrophages), and OX6 (antigen-presenting cells) were evaluated. There were no differences in macrophage numbers among the anatomical sites. In the epidermis, only OX6 cells were seen, with gradually increased numbers in neonates and adults. In the dermis, many ED1 cells were already seen in fetuses, and the number peaked on neonatal day 4, and remained at that level until adulthood. By contrast, ED2 and OX6 cells began to be seen after birth and their numbers continued to increase until adulthood; ED2 cells were distributed diffusely in the dermis, whereas ED1 and OX6 cells were present exclusively in the upper dermis. In perifollicular areas, ED1, ED2 and OX6 cells began to be seen after birth, and their numbers gradually increased until adulthood. Some macrophages in dermal and perifollicular areas gave double-positive reactions to ED1+ED2+, ED1+OX6+ or OX6+ED2+. Increased mRNA levels of colony stimulating factor-1 and monocyte chemoattractant protein-1 appeared to correspond to the emergence of rat macrophages. Skin macrophages were shown to be heterogeneous in distribution and function; the information from this study should be very useful for future investigations of experimentally induced rat skin lesions.