Surfactant Regulation of Lung Immune Cell Function

The major area of investigation in my laboratory is the regulation of immune cell function by pulmonary surfactant. In the lung, there are mechanisms for host-defense similar to those that are operational elsewhere in the body, but there are also mechanisms that are unique to the lung. Some of these additional mechanisms involve pulmonary surfactant. There is mounting evidence that the surfactant proteins, SP-A and SP-D, both of which are collagenous C-type lectins or collectins, have immunoregulatory roles. The regulation of SP-A is very complex. Its levels in the alveolus change in response to a variety of hormones, several different cytokines, and a diverse collection of environmental stimuli. We are currently continuing our studies of the regulation of SP-A using a lung epithelial cell line and various animal models.

Both SP-A and SP-D are involved in the recognition of some microorganisms. In some cases these proteins function as opsonins and stimulate chemotaxis and phagocytosis. However, there is considerable selectivity in this process. The effects of each of these proteins vary depending on the type of microorganism, the specific strain of bacteria involved, the growth phase of the pathogen, and the phagocytic cell type tested. The effects of SP-A on several other aspects of immune cell function have also been investigated in several different types of immune cells, particularly those of the monocyte/macrophage lineage. These effects include increased proliferative activity in response to different stimuli, the enhanced production of proinflammatory cytokines, increased immunoglobulin secretion, and the expression of cell surface molecules related to inflammation.

Recently, we have begun to explore the mechanisms behind these effects and have found that SP-A exerts its effects, at least in part, by activating the transcriptional regulator, NF-kB. SP-A exerts stimulatory effects on all of the parameters mentioned earlier. However, the predominant surfactant lipids have inhibitory or anti-inflammatory effects. These opposite effects on immune cell function by different surfactant components suggest that the relative abundance of various surfactant components in the alveolar lining material determines the functional status of immune cells in the lung. These studies also raise the possibility that alterations in surfactant could play a role in the pathogenesis of some lung diseases involving immune cells.