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

have undertaken a series of studies to elucidate the roles of growth factor s (FGF-2, EGF, TGF-beta 1) and prolactin (PRL) in lacrimal gland function d uring pregnancy and lactation, and to better understand the status of the i mmune system within the lacrimal gland during those physiological states. I n this initial study, lacrimal glands of pregnant (d15, d29), lactating (9d , 22d), and adult female control rabbits, were evaluated by immunohistochem istry, Western blotting and image analysis. In control rabbits EGF, TGF-bet a 1 and PRL, were immunolocalized primarily in the apical cytoplasm of intr alobular ductal epithelial cells, and acini demonstrated a basement membran e-associated immunopositivity for TGF-beta 1. FGF-2 immunolocalized in myoe pithelial cells in the basal ductal epithelium and complexed to the basemen t 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 ECF and TGF-beta 1 was increas ed within intralobular ducts, both apically and basally, and within some in terlobular ductal epithelial cells. Immunopositivity for PRL was strongest in d29 pregnant rabbits within the epical and basal cytoplasm of intralobul ar ductal epithelial cells. Immunopositivity, for FGF-2, in myoepithelial c ells was strong in d15 and d29 pregnant rabbits, although basement membrane -associated immunopositivity around acini was often decreased. Immunostaini ng for EGF and TGF-beta 1 in lactating rabbits was similar to that in d29 p regnant rabbits, although basement membrane-associated immunopositivity aro und acini was more comparable to controls, By 22d lactation immunopositivit y for FGF-2 closely resembled that in controls. Image analysis of pregnant and lactating rabbits demonstrated that cells immunopositive for RTLA and C D18 were less abundant around ducts and more abundant between acini, althou gh in 22d lactating rabbits the size of periductal foci was increased to ne arly that of controls, Western blots correlated well with the immunohistoch emistry. Our findings demonstrate that pregnancy and lactation are accompan ied by a shift in the distributions of growth factors and PRL, suggestive o f increased release both apically into the lacrimal fluid and basally into the interstitium. Additional shifts in the distributions of cells of the im mune system from periductal foci to interacinar sites suggest that there is a recruitment of immune cells away from ducts and toward the connective ti ssue interstitium surrounding the acini, possibly as part of a heightened s tate of immune readiness during pregnancy and lactation. (C) 2000 Academic Press.