A Primate Model of Neonatal Lung Defense Mechanisms

Boldt, David

Abstract

A baboon model will be employed to support 2 projects designed to study local pulmonary defense mechanisms during perinatal development: 1) pulmonary macrophage function; and, 2) the barrier function of respiratory tract epithelial surfaces. The fetal baboon will be studied at 3 time points during the third trimester, at term, and at 1 month after birth. Project 1 will establish the time frame for appearance of pulmonary macrophages (PM) in lung interstitium and alveolar spaces. A primary focus will be to define functional capabilities of PM during the third trimester and first month of life. This will include examination of their phagocytic and microbicidal potential, capacity for generation of immunocompetent lymphocytes, and role in antigen processing. Gamma-interferon will be studied for its ability to enhance certain PM functions. Monoclonal antibodies specific for baboon lymphocytes will be produced and they will be used to identify specific lymphocyte subclasses present in the developing lung and to define interactions of these cells with PM. The respiratory tract epithelium and its secretions form a barrier against potential pathogens present in the external environment and they protect the host from colonization and infection. Project 2 will study developmental changes in the respiratory tract epithelium by measuring surface carbohydrate patterns. These patterns will be correlated with bacterial adherence to the epithelium. Effects of respiratory tract secretions on bacterial binding also will be examined. A baboon neonatal intensive care unit capable of providing services similar to those provided for human prematures is available for this project. Therefore, we plan to study effects of premature delivery and intensive life support (high p02, incubation, mechanical ventilation) on both PM function and also the barrier function of the respiratory epithelium in a group of mid-third trimester fetal baboons.