NEUTROPHIL DEACTIVATION BY INFLUENZA-A VIRUSES - MECHANISMS OF PROTECTION AFTER VIRAL OPSONIZATION WITH COLLECTINS AND HEMAGGLUTINATION-INHIBITING ANTIBODIES

Bacterial superinfections are a major cause of morbidity and mortality during influenza A virus (IAV) epidemics. Depression of phagocyte fun ctions resulting from attachment of the IAV hemagglutinin (HA) to cell surface sialo-glycoproteins is a likely contributory cause of these i nfections. We have proposed that the group of collagenous lectins (ter med collectins) present in blood and pulmonary surfactant play a role in initial host defense against IAV. We used here several recombinant human surfactant protein D (RhSP-D) preparations to determine the mech anism through which opsonization of IAV with collectins protects neutr ophils against the deactivating effects of IAV on cellular respiratory burst responses in vitro. RhSP-D was markedly more potent than antibo dies that inhibited viral hemagglutination activity (anti-HA antibodie s) at protecting neutrophils in this assay. Unlike the anti-HA antibod ies, RhSP-D was protective at concentrations that minimally inhibited viral hemagglutination activity. Two related features of SP-D-the degr ee of multimerization and the ability to cause aggregation of IAV part icles-were critical determinants of the ability of SP-D to protect neu trophils against deactivation. Similarly SP-D-induced viral aggregate formation resulted in enhanced IAV binding to neutrophils and potentia ted the ability of the virus itself to trigger neutrophil respiratory burst responses. In contrast to the case of IAV-antibody complexes, SP -D-IAV complexes attached to and activated neutrophils through a neura minidase-sensitive mechanism (ie, similar to unopsonized IAV). These r esults indicate that collectin-mediated viral aggregation per se may b e an important host defense mechanism not only by virtue of reducing t he number of infectious viral particles, but also by promoting phagocy te responsiveness. (C) 1996 by The American Society of Hematology.