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Am. J. Respir. Cell Mol. Biol., Volume 24, Number 4, April, 2001 452-458

Alveolar Macrophages, Surfactant Lipids, and Surfactant Protein B Regulate the Induction of Immune Responses via the Airways

J. Freek van Iwaarden, Eric Claassen, Suzan H. M. Jeurissen, Henk P. Haagsman, and Georg Kraal

Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam; Laboratory of Pediatrics, Erasmus University Rotterdam, Rotterdam; Institute for Animal Science and Health, Lelystad; and Laboratory of Veterinary Biochemistry, Utrecht University, Utrecht, The Netherlands

The influences of alveolar macrophages (AM) and pulmonary surfactant on the induction of immune responses via the airways were assessed. Mice were depleted of their AM by intratracheal instillation of multilamellar vesicles containing dichloromethylene-diphosphonate followed by intratracheal instillation of a T cell-dependent antigen, trinitrophenyl-keyhole limpet hemocyanin, in vesicles of various compositions. The primary immune response was determined in the spleen of these animals using an ELI-Spot assay. The secondary immune responses in the sera of the mice were assessed using enzyme-linked immunosorbent assays. An immune response was detected in animals depleted of their AM and intratracheally instilled with antigen in small unilamellar vesicles consisting of either phosphatidylcholine cholesterol or surfactant lipids. Incorporation of surfactant protein (SP)-B in the antigen vesicles enhanced the immune response, whereas SP-A or SP-C in the antigen vesicle did not have an effect. Strikingly, intratracheal instillation of SP-B containing antigen vesicles can induce an immunoglobulin M immune response in mice without depletion of AM. These results indicate that SP-B containing vesicles can enhance the induction of immune responses via the airways and further illustrate the important roles of both AM and pulmonary surfactant in the pulmonary immune system.

Abbreviations: bovine serum albumin, BSA; dichloromethylene-diphosphonate, DMDP; enzyme-linked immunosorbent assay, ELISA; immunoglobulin, Ig; multilamellar vesicles, MLV; phosphate-buffered saline, PBS; Tween-20 in PBS, PBT; phosphatidylcholine, PC; phosphatidylglycerol, PG; surfactant protein, SP; small unilamellar vesicles, SUV; trinitrophenyl-keyhole limpet hemocyanin, TNP-KLH; trinitrophenyl-ovalbumin, TNP-OVA.




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