Distribution of growth factors and immune cells are altered in the lacrimal gland during pregnancy and lactation.

We have undertaken a series of studies to elucidate the roles of growth factors (FGF-2, EGF, TGF-beta1) and prolactin (PRL) in lacrimal gland function during pregnancy and lactation, and to better understand the status of the immune system within the lacrimal gland during those physiological states. In this initial study, lacrimal glands of pregnant (d15, d29), lactating (9d, 22d), and adult female control rabbits, were evaluated by immunohistochemistry, Western blotting and image analysis. In control rabbits EGF, TGF-beta1, and PRL, were immunolocalized primarily in the apical cytoplasm of intralobular ductal epithelial cells, and acini demonstrated a basement membrane-associated immunopositivity for TGF-beta1. FGF-2 immunolocalized in myoepithelial cells in the basal ductal epithelium and complexed to the basement membrane enclosing ducts and acini. Cells immunopositive for immune cell markers (RTLA and CD18) were apparent primarily around interlobular ducts. In d29 pregnant rabbits immunopositivity for EGF and TGF-beta1 was increased within intralobular ducts, both apically and basally, and within some interlobular ductal epithelial cells. Immunopositivity for PRL was strongest in d29 pregnant rabbits within the apical and basal cytoplasm of intralobular ductal epithelial cells. Immunopositivity for FGF-2 in myoepithelial cells was strong in d15 and d29 pregnant rabbits, although basement membrane-associated immunopositivity around acini was often decreased. Immunostaining for EGF and TGF-beta1 in lactating rabbits was similar to that in d29 pregnant rabbits, although basement membrane-associated immunopositivity around acini was more comparable to controls. By 22d lactation immunopositivity for FGF-2 closely resembled that in controls. Image analysis of pregnant and lactating rabbits demonstrated that cells immunopositive for RTLA and CD18 were less abundant around ducts and more abundant between acini, although in 22d lactating rabbits the size of periductal foci was increased to nearly that of controls. Western blots correlated well with the immunohistochemistry. Our findings demonstrate that pregnancy and lactation are accompanied by a shift in the distributions of growth factors and PRL, suggestive of increased release both apically into the lacrimal fluid and basally into the interstitium. Additional shifts in the distributions of cells of the immune system from periductal foci to interacinar sites suggest that there is a recruitment of immune cells away from ducts and toward the connective tissue interstitium surrounding the acini, possibly as part of a heightened state of immune readiness during pregnancy and lactation. Copyright 2000 Academic Press.