Macrophages serve as the first line of defense in the lung and play a pivotal role in many aspects of lung inflammation. Our long-term objective is to study the source of macrophages in the lung and the means by which their numbers are controlled. In this proposal, we will attempt to isolate and characterize a subset of alveolar macrophages that are capable of extensive replication and forming colonies in vitro (alveolar macrophage colony-forming cells, AL-CFC). We will produce a monoclonal antibody specific for AL-CFC. The antibody will be used to isolate AL-CFC with the aid of a fluorescence-activated cell sorter. We will characterize AL-CFC according to cell size, morphology, ultrastructure, phagocytosis, enzymatic activity and presence of surface receptors. We will also develop a monoclonal antibody specific for colony-stimulating factor (CSF-1). AL-CFC require CSF-1 for growth and appear to have receptors for CSF-1. We will use anti-CSF-1 antibody to isolate AL-CFC. The origin of AL-CFC in radiation-induced chimera, we will investigate by using different whole-body irradiation techniques.