Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses.

Abstract

We tested the hypothesis that pulmonary surfactant-associated lectins -surfactant proteins A and D (SP-A, and -D) contribute to initial protective mechanisms against influenza A viruses (IAVs). SP-D potently inhibited hemagglutination activity of several strains of IAV as well as causing viral aggregation. SP-D enhanced neutrophil binding of 1AV and neutrophil respiratory burst responses to the virus. Neutrophil dysfunction resulting from 1AV exposure was diminished when the virus was pre-incubated with SP-D. Each of these effects was mediated by the calcium-dependent carbohydrate-binding property of SP-D. Native SP-D preparations of both human and rat origin, as well as recombinant rat SP-D, had similar activity. SP-A also inhibited IAV hemagglutination activity. We have previously reported that related mammalian serum lectins (mannose-binding lectin [MBL] and conglutinin) have similar effects. SP-D was at least 10-fold more potent at causing hemagglutination inhibition than were SP-A or MBL. SP-D was shown to contribute to potent anti-IAV activity of human bronchoalveolar lavage fluid. These results suggest that SP-D-alone, and in conjunction with SP-A and phagocytic cells-constitutes an important component of the natural immune response to 1AV infection within the respiratory tract. (J. Clin. Invest.

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

“…SP-D, a collectin present in respiratory fluids, and the short pentraxin SAP bind to influenza viruses in a Ca 2ϩ -dependent manner (4,6,22,23) and mediate antiviral activity by binding to mannose residues on the viral HA/NA glycoproteins. Therefore, studies were undertaken to assess the ability of the long pentraxin PTX3 to bind influenza virus by ELISA.…”

“…Both surfactant protein-A (SP-A) and SP-D mediate a range of activities against influenza virus, including inhibition of hemagglutination, virus neutralization, virus aggregation, and opsonizaton of the virus for interaction with neutrophils (2)(3)(4)(5)(6)(7)(8), with SP-D acting as a more potent inhibitor than SP-A in vitro (4). Levels of SP-D recovered from the airways by lavage increase significantly following infection of mice with influenza virus (3, 9 -11), and SP-D Ϫ/Ϫ mice exhibit enhanced viral replication and illness (9,11).…”

“…SP-D functions as a classic ␤ inhibitor, binding in a Ca 2ϩ -dependent manner through its lectin domains to oligosaccharides on the viral hemagglutinin (HA) and neuraminidase (NA) glycoproteins (6). As such, the degree or pattern of glycosylation is a major factor in determining the sensitivity of a particular virus strain to inhibition by SP-D (3).…”

Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus

“…Innate immune proteins within the respiratory tract, including the pulmonary collectins, surfactant proteins D and A (SP-D and SP-A), and lung scavenger receptor-rich glycoprotein-340 (lung gp-340), have strong IAV neutralizing and aggregating activity (4, 14 -16, 19, 30, 34, 35). Among the known human collectins, SP-D has the strongest in vitro IAV neutralizing and aggregating activity (19). Removal of SP-D from bronchoalveolar lavage (BAL) fluid significantly reduced antiviral activity (19).…”

“…Among the known human collectins, SP-D has the strongest in vitro IAV neutralizing and aggregating activity (19). Removal of SP-D from bronchoalveolar lavage (BAL) fluid significantly reduced antiviral activity (19). SP-D knockout mice exhibit greatly increased viral titers, lung inflammation, and illness after infection with IAV (26,35).…”