Inflammatory lung injury is a significant cause of morbidity or mortality. Recent evidence suggests 1) that accumulation of neutrophils (PMN) in the lungs is associated with acute as well as chronic inflammatory lung injury and 2) that alveolar macrophages (AM) may release mediators that recruit and activate PMN in the lungs. Recognizing the potential detrimental consequences associated with the accumulation and activation of PMN in the lung as well as the need for controlling and delimiting inflammatory responses; one might speculate that mechanisms exist which under normal circumstances decrease or suppress PMN recruitment and activation in the lung. This premise is supported by the observation that PMN are rarely present in the extravascular space of the lungs. To address this possibility we hypothesized that under normal conditions, AM release factors that suppress recruitment and activation of PMN in the lung. Our preliminary findings have supported this premise by showing that supernatants from unstimulated AM contain factors that decrease PMN chemotaxis, adherence and oxygen radical production. Our immediate specific aims are: 1. To determine and partially characterize factors released by AM in vitro then suppress PMN function in vitro. 2. To determine if these factors exist in vivo. 3. To determine if in vivo PMN suppressor factors are biochemically similar to in vitro AM derived PMN suppressor factors. Since PMN can injure the lung, suppression of needless PMN recruitment to and activation in the lung may be essential to maintaining healthy lungs. Furthermore, defects in AM synthesis and/or release of PMN suppressor factors may well be the basis of certain inflammatory disease.
