The Role of Surfactant-Associated Protein A in Pulmonary Host Defense

Abstract

Resident alveolar macrophages play a key role in the initial defense against inhaled pathogens. Surface molecules bind opsonized as well as nonopsonized microbes and mediate their internalization by the macrophage. The recent discovery that specific C-type lectins can bind to the surface of a wide range of pathogens has led to the hypothesis that these lectins are involved in the initial phases of microbe recognition by the macrophage. Studies in our laboratory focus on the role of the lung-specific lectin surfactant associated protein A (SP-A) in host defense against pulmonary pathogens. SP-A contains a carbohdyrate recognition domain that appears to bind specifically to exposed carbohydrate residues on the surface of microorganisms. This lectin-microorganism interaction leads to entry of specific pathogens into macrophages and activation of intracellular pathways, resulting in the production of antimicrobial mediators such as nitric oxide. Many studies, including those involving SP-A-deficient mice, underscore the importance of this protein in pulmonary innate immunity. However, the intramacrophage mechanisms underlying the effects of SP-A are still unclear. This article describes our current knowledge of SP-A and its interactions with immune cells and pathogens with a focus on recent findings from our laboratory regarding SP-A interactions with mycobacteria.

Cutting Edge: The Immunostimulatory Activity of the Lung Surfactant Protein-A Involves Toll-Like Receptor 4

“…A growing number of reports have suggested that SP-A may have some host defense-related properties (3,4). We first sought to characterize the effect of purified SP-A on murine BMDM, in terms of cytokine production.…”

“…However, there are also proteins associated with the surface-active material. The most abundant among them, surfactant protein-A (SP-A), 3 is a member of the collectin family of preimmune opsonins, which also includes surfactant protein-D, mannose-binding protein, conglutinin, and collectin-43 (1,2). Recent studies suggest an integral role for SP-A in innate host defense and regulation of inflammatory processes in the lung.…”

“…Recent studies suggest an integral role for SP-A in innate host defense and regulation of inflammatory processes in the lung. Although several studies have demonstrated that SP-A enhances macrophage chemotaxis, phagocytosis, immune cell proliferation, and expression of cell surface proteins, the role of SP-A in regulating production of cytokines is controversial (3)(4)(5)(6)(7)(8)(9). Regardless, the observation that SP-A can mediate cell-specific functions suggests the existence of specific receptors.…”

Bacterial Pneumonia and Lung Abscess

“…9 In the distal airways and alveoli, pulmonary surfactant proteins A and C can inhibit bacterial binding to host cells and also promote phagocytosis of selected bacteria. 10,11 The presence of complement and immunoglobulins (particularly immunoglobulin A [IgA]), also prevents colonization of the oropharynx. In addition to protection provided by host factors, the upper airway microbiota may modulate susceptibility to pathogens, as indicated by the evidence that broad-spectrum antimicrobial therapy predisposes to colonization and infection.…”

Untitled

“…Surfactant plays an increasingly recognized role in immune defence. Surfactant protein (SP)-A is known to promote phagocytosis of bacteria by alveolar macrophages, and SP-D also has antimicrobial properties [96,97]. Deficiency in these specific proteins may well contribute to the increase risk for infection in ARDS patients.…”