Surfactant protein A enhances the phagocytosis of C1q-coated particles by alveolar macrophages

Abstract

Surfactant protein-A (SP-A) plays multiple roles in pulmonary host defense, including stimulating bacterial phagocytosis by innate immune cells. Previously, SP-A was shown to interact with complement protein C1q. Our goal was to further characterize this interaction and elucidate its functional consequences. Radiolabeled SP-A bound solid-phase C1q but not other complement proteins tested. The lectin activity of SP-A was not required for binding to C1q. Because C1q is involved in bacterial clearance but alone does not efficiently enhance the phagocytosis of most bacteria, we hypothesize that SP-A enhances phagocytosis of C1q-coated antigens. SP-A enhanced by sixfold the percentage of rat alveolar macrophages in suspension that phagocytosed C1q-coated fluorescent beads. Furthermore, uptake of C1q-coated beads was enhanced when either beads or alveolar macrophages were preincubated with SP-A. In contrast, SP-A had no significant effect on the uptake of C1q-coated beads by alveolar macrophages adhered to plastic slides. We conclude that SP-A may serve a protective role in the lung by interacting with C1q to enhance the clearance of foreign particles.

Complement levels and activity in the normal and LPS-injured lung

“…Buffers were as follows: isotonic veronal-buffered saline (VBS) with metals and gelatin (GVBS ϩ/ϩ ), prepared as previously described (45,48); EDTA-GVBS Ϫ/Ϫ , made without MgCl2 or CaCl2 and containing 0.01 M EDTA; EGTA-GVBS ϩ/ϩ , containing 5 mM MgCl2 and 8 mM EGTA; Dulbecco's phosphate-buffered saline (DPBS; Sigma-Aldrich, St. Louis, MO); and Tris-buffered saline (TBS; 20 mM Tris base, 137 mM NaCl, 3.8 mM HCl, pH 7.6).…”

Eosinophil-Associated Lung Diseases. A Cry for Surfactant Proteins A and D Help?

“…SP-A has been shown to enhance phagocytosis of IgG-opsonized particles (23) and complement-coated particles (24) and to preferentially bind apoptotic neutrophils, which aides in their removal from the inflamed lung (25,26). SP-D is known to aggregate and aid in the removal of pollen starch granules (27,28), to bind and enhance clearance of genomic DNA and apoptotic cells (29), and to aggregate and remove nanoparticles (30).…”

Macrophages – Balancing Tolerance and Immunity

“…Phagocytosis of apoptoic neutrophils by AMs (but not peritoneal macrophages) can be dramatically enhanced by surfactant A opsonization, but not by MBL and C1q [242]. However, surfactant A significantly enhances the uptake of C1q-coated particles by AMs [243]. There remains an unresolved debate as to what determines whether the phagocytic uptake of apoptotic cells will be anti-or proinflammatory.…”

“…Equally, in the later stages of immune responses, phagocytosis of apoptotic neutrophils could tip the balance back again towards antiinflammation'. Thus, neutrophils when in proinflammatory mode' may be viewed as pre-amplifiers' of a proinflammatory input to the MDU, but when in apoptotic mode', may provide an input tending to polarize the MDU away from proinflammation and towards antiinflammation [243,574]. Mechanisms of innate tolerance are of particular interest in tissues resistant to inflammation such as brain (where microglia constitute the resident macrophages) [575,576] and the anterior chamber of the eye, where even minor inflammation may be catastrophic.…”