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

1 Department of Medicine, Section of Hematology/Oncology, Boston University School of Medicine, Boston Massachusetts; 2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; 3 Department of Biochemistry and Cell Biology, Utrecht University Faculty of Veterinary Medicine, Utrecht, Netherlands; and 4 Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark Submitted 23 March 2005 ; accepted in final form 5 June 2005 Oxidants and neutrophils contribute to lung injury during influenza A virus (IAV) infection. Surfactant protein (SP)-D plays a pivotal role in restricting IAV replication and inflammation in the first several days after infection. Despite its potent anti-inflammatory effects in vivo, preincubation of IAV with SP-D in vitro strongly increases neutrophil respiratory burst responses to the virus. Several factors are shown to modify this apparent proinflammatory effect of SP-D. Although multimeric forms of SP-D show dose-dependent augmentation of respiratory burst responses, trimeric, single-arm forms either show no effect or inhibit these responses. Furthermore, if neutrophils are preincubated with multimeric SP-D before IAV is added, oxidant responses to the virus are significantly reduced. The ability of SP-D to increase neutrophil uptake of IAV can be dissociated from enhancement of oxidant responses. Finally, several other innate immune proteins that bind to SP-D and/or IAV (i.e., SP-A, lung glycoprotein-340 or mucin) significantly reduce the ability of SP-D to promote neutrophil oxidant response. As a result, the net effect of bronchoalveolar lavage fluids is to increase neutrophil uptake of IAV while reducing the respiratory burst response to virus. surfactant protein D; surfactant protein A; collectin; glycoprotein-340; bispecific protein Address for reprint requests and other correspondence: K. L. Hartshorn, Boston Univ. School of Medicine, EBRC 414, 650 Albany St., Boston, MA 02118 (e-mail: khartsho{at}bu.edu )