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Am. J. Respir. Cell Mol. Biol., Volume 23, Number 5, November, 2000 586-592

Surfactant Protein-A Enhances Uptake of Respiratory Syncytial Virus by Monocytes and U937 Macrophages

Frederick E. Barr, Heather Pedigo, Teresa R. Johnson, and Virginia L. Shepherd

Pediatric Critical Care and Anesthesia, Vanderbilt Children's Hospital, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

Surfactant protein (SP)-A is a known opsonin for a variety of pulmonary pathogens. SP-A enhances ingestion of these pathogens by interaction with an SP-A receptor (SP-AR) found on phagocytic cells such as peripheral blood monocytes (PBMC) and alveolar macrophages. Respiratory syncytial virus (RSV) is the most important respiratory pathogen in children. Recent studies have indicated that SP-A levels may be decreased in RSV bronchiolitis and pneumonia. In this study we examined the role of SP-A in uptake of RSV by both PBMC and U937 macrophages, a human macrophage cell line known to express SP-ARs. In addition, we studied the effect of SP-A- mediated uptake of RSV on production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 by these cells because incomplete immunity to recurrent RSV infection has been partially attributed to abnormal cytokine responses by macrophages. SP-A enhanced binding and uptake of fluorescently labeled RSV (RSV-FITC) by PBMC in a dose-dependent manner, with a maximal effect seen with 10 to 15 µg/ml SP-A as measured by both percent fluorescent monocytes and linear mean fluorescence (lmf) of individual cells. SP-A also enhanced uptake of RSV-FITC by U937 macrophages, with a maximal effect seen with 20 µg/ml SP-A as measured by both percent fluorescent monocytes and lmf. With respect to TNF-alpha levels, RSV alone slightly enhanced TNF-alpha production by PBMC and decreased TNF-alpha production by U937 macrophages measured at 12 h after addition of RSV. SP-A-mediated uptake of RSV significantly enhanced TNF-alpha production by PBMC and reversed the RSV-induced depression of TNF-alpha by U937 macrophages. RSV significantly enhanced IL-10 production by both cell types, which was reversed by SP-A-mediated uptake. These findings suggest that SP-A is an important opsonin for RSV and that SP-A-mediated uptake of RSV may alter some of the unusual cytokine responses that are postulated to be involved in incomplete immunity to recurrent infection.




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