Surfactant protein A stimulates phagocytosis of specific pulmonary pathogens by alveolar macrophages

Abstract

Surfactant protein A (SP-A) regulates alveolar macrophage function and has been implicated in the mediation of pulmonary host defense. Our goals were to characterize the interaction of SP-A with various pulmonary pathogens, to investigate the mechanism of SP-A-mediated phagocytosis using an assay that distinguishes bound from internalized bacteria by quenching the fluorescence of extracellular bacteria, and to examine further the interactions of SP-A and the structurally homologous protein complement component 1q (C1q) with alveolar macrophages and peripheral blood monocytes. We found that SP-A binds to and increases the phagocytosis of Haemophilus influenzae, Streptococcus pneumoniae, and Group A Streptococcus; SP-A aggregates only H. influenzae. SP-A neither binds to, aggregates, nor stimulates the phagocytosis of Pseudomonas aeruginosa. We have also found that bronchoalveolar lavage stimulates phagocytosis and that this stimulation is reduced by an anti-SP-A antibody. While the enhancement of phagocytosis by SP-A is inhibited in blood monocytes adhered to C1q-coated surfaces, which presumably clusters the C1q receptor on the basal surface of the cell, alveolar macrophages on C1q-coated slides show no significant change in their response to SP-A. In summary, SP-A stimulates the phagocytosis by alveolar macrophages of specific pulmonary pathogens to which it binds, but aggregation is not required for the effect. Additionally, the role of the C1q receptor in the response to SP-A may differ between monocytes and alveolar macrophages.

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

“…Because SP-A has been shown to interact with both bacteria and macrophages, we opted in this study to mimic, to the greatest extent possible, the native conditions and avoid any potential modifications of both bacteria and macrophages. Therefore, the present findings may be more reflective of in vivo occurrences due to the use of live, nonlabeled, freshly isolated P. aeruginosa rather than use of heat-killed or FITC-labeled bacteria (34,47,60) as discussed above.…”

“…When heat-killed P. aeruginosa bacteria were used, hSP-A from BAL did not enhance phagocytosis (60). This result could be associated with changes in the surface properties of the bacteria resulting from heat killing.…”

The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

“…While immobilized C1q was shown to enhance FcR-and CRmediated phagocytosis by macrophages, it was shown to inhibit monocyte phagocytosis of surfactant protein A (SP-A)-opsonized bacteria (101). This was not observed with alveolar macrophages (101). Like MBL, SP-A is a member of the collectin family (6).…”

“…Like MBL, SP-A is a member of the collectin family (6). The mechanism of this inhibition is unclear (101).…”

Isolation and characterization of a fish F-type lectin from gilt head bream (Sparus aurata) serum

“…In vertebrates, the role of lectins as mediators of self and non-self recognition in early development and innate immunity has been well documented [2][3][4][5]. The presence of multiple CRDs in combination with other protein domains, enable not only the recognition of carbohydrates on the surface of potential pathogens, but also effector functions including agglutination, immobilization and opsonization of potential pathogens, and activation of the complement pathway [6][7][8].…”