Pulmonary Surfactant: An Immunological Perspective

Abstract

Pulmonary surfactant has two crucial roles in respiratory function; first, as a biophysical entity it reduces surface tension at the air water interface, facilitating gas exchange and alveolar stability during breathing, and, second, as an innate component of the lung's immune system it helps maintain sterility and balance immune reactions in the distal airways.

Early Alveolar Epithelial Dysfunction Promotes Lung Inflammation in a Mouse Model of Hermansky-Pudlak Syndrome

“…SP-D has emerged as a key modulator of inflammation in the alveolar space (36). In its multimeric form, the lectin-binding domains interact with surface receptors such as SIRPa on effector cells, attenuating NF-kBmediated proinflammatory gene expression (37). In a variety of models of pulmonary inflammation using exogenous inflammatory stimuli (bleomycin, Pneumocystis), we have shown previously that alveolar inflammation leads to local production of NO metabolites via increased iNOS expression by activated macrophages, promoting S-nitrosylation of SP-D and disrupting SP-D tertiary structure (9,15).…”

Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

“…SP-A is the major protein constituent of pulmonary surfactant; it is involved in organization of large aggregate surfactant phospholipids lining the alveolar surface and acts as an opsonin for pathogens (7). SP-A is incorporated in the tubular myelin fraction of pulmonary surfactant that covers the alveolar lining fluid of the distal airway epithelium.…”

Toll-like Receptor 2 (TLR2), Transforming Growth Factor-β, Hyaluronan (HA), and Receptor for HA-mediated Motility (RHAMM) Are Required for Surfactant Protein A-stimulated Macrophage Chemotaxis

“…Toll-like receptors (TLRs) 3 and a family of proteins called collectins play central roles in regulation of host defense via recognition of specific pathogen-associated molecular patterns (PAMPs) on various microorganisms (1). Although these innate immune receptors are widely expressed, they are of particular importance to dendritic cells and macrophages.…”

“…They have important roles in aggregation, opsonization, and phagocytosis of pulmonary pathogens, as well as production of reactive oxygen species and cytokines (3,4). In particular, SPA stimulates macrophage chemotaxis (5) and phagocytosis of apoptotic neutrophils, mechanisms that result in production of TGF␤ (6).…”