title: Bovine peptidoglycan recognition protein-S: antimicrobial activity, localization, secretion, and binding properties.
abstract: Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern recognition molecules of innate immunity that are conserved from insects to humans. Various PGRPs are reported to have diverse functions: they bind bacterial molecules, digest PGN, and are essential to the Toll pathway in Drosophila. One family member, bovine PGN recognition protein-S (bPGRP-S), has been found to bind and kill microorganisms in a PGN-independent manner, raising questions about the identity of the bPGRP-S ligand. Addressing this, we have determined the binding and microbicidal properties of bPGRP-S in a range of solutions approximating physiologic conditions. In this study we show that bPGRP-S interacts with other bacterial components, including LPS and lipoteichoic acid, with higher affinities than for PCP, as determined by their abilities to inhibit bPGRP-S-mediated killing of bacteria. Where and how PGRPs act in vivo is not yet clear. Using Immunogold electron microscopy, PGRP-S was localized to the dense/large granules of naive neutrophils, which contain the oxygen-independent bactericidal proteins of these cells, and to the neutrophil phagolysosome. In addition, Immunogold staining and secretion studies demonstrate that neutrophils secrete PGRP-S when exposed to bacteria. Bovine PGRP-S can mediate direct lysis of heat-killed bacteria; however, PGRP-S-mediated killing of bacteria is independent of this activity. Evidence that bPGRP-S has multiple activities and affinity to several bacterial molecules challenges the assumption that the PGRP family of proteins recapitulates the evolution of TLRs. Mammalian PGRPs do not have a single antimicrobial activity against a narrow range of target organisms; rather, they are generalists in their affinity and activity.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA. chacetyd@caltech.edu
authors.forename: C Chace
authors.initials: CC
authors.lastname: Tydell
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Patti
authors.initials: P
authors.lastname: Tran
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selsted
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000378:metabolism; D008089:Listeria monocytogenes / Q000187:drug effects; D016253:Microscopy, Immunoelectron; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D010457:Peptidoglycan / Q000378:metabolism; D011485:Protein Binding; D012486:Salmonella typhimurium / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein