title: Partially opened triple helix is the biologically active conformation of 1-->3-beta-glucans that induces pulmonary inflammation in rats.
abstract: 1-->3-beta-Glucans produce pulmonary inflammation in rats and are commonly found in indoor air dust samples. Conformation is an important factor determining the biological activity of 1-->3-beta-glucans. The partially opened triple-helix conformation induced by NaOH treatment and the annealed triple-helix conformation have been identified by fluorescence resonance energy transfer spectroscopy in our previous study. The objective of this study was to examine the role of these conformations of 1-->3-beta-glucans in the induction of pulmonary inflammation in rats. A partially opened triple-helix conformation of the known inflammatory 1-->3-beta-glucan zymosan was prepared by treating zymosan with NaOH followed by neutralization and dialysis. The annealed triple-helix conformation was prepared by allowing the partially opened triple-helix conformation to anneal for 9 d at room temperature. Rats were exposed to fresh or annealed NaOH-treated zymosan via intratracheal instillation. The results show that the zymosan-induced pulmonary inflammatory responses were significantly reduced after the 9-d annealing period, which suggests that this inflammatory response was dependent on the conformation of zymosan. Freezing NaOH-treated zymosan (for 7 d) inhibited the annealing process. Exposure of rats to thawed preparations of zymosan resulted in the same inflammatory responses as the freshly prepared partially opened triple-helix zymosan. In contrast, the potency of untreated zymosan did not change significantly following a 7-d annealing period, indicating that annealing occurs only after the conformation has been modified by NaOH treatment. This study indicates that the partially opened triple helix of 1-->3-beta-glucans is more active than the closed conformation in inducing pulmonary inflammation in rats.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA. shih-houng_young@msn.com
authors.forename: Shih-Houng
authors.initials: SH
authors.lastname: Young
authors.forename: Victor A
authors.initials: VA
authors.lastname: Robinson
authors.forename: Mark
authors.initials: M
authors.lastname: Barger
authors.forename: David G
authors.initials: DG
authors.lastname: Frazer
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D005936:Glucans / Q000009:adverse effects* / Q000737:chemistry*; D008297:Male; D011014:Pneumonia / Q000503:physiopathology* / Q000662:veterinary; D051381:Rats; D017207:Rats, Sprague-Dawley; D012972:Sodium Hydroxide / Q000737:chemistry; D013329:Structure-Activity Relationship; D015054:Zymosan / Q000494:pharmacology
chemical_list: D005936:Glucans; D012972:Sodium Hydroxide; D015054:Zymosan