(1→3)-β-D-glucan derivatives with unique structural properties differentially affect murine lung inflammation and histology

Author:

Metwali N.ORCID,Stapleton E.M.ORCID,Hadina S.ORCID,Thorne P.S.ORCID

Abstract

ABSTRACTBackgroundβ-D-glucan (BDG) compounds are proinflammatory fungal cell wall polysaccharides known to cause respiratory pathology. However, the specific immunological effect of unique BDG structures on pulmonary inflammation is understudied. We sought to characterize the effect of four unique fungal BDGs with unique branching patterns, solubility, molecular weights and higher order structure in murine airways.MethodsScleroglucan (1→3) (1→6)-highly branched BDG, laminarin (1→3) (1→6)-branched BDG, curdlan (1→3)-linear BDG, and pustulan (1→6)-linear BDG were assessed by nuclear magnetic resonance spectroscopy (NMR). Glucan compounds were confirmed negative for endotoxin by kinetic chromogenic Limulus amebocyte lysate assay. Each BDG was tested using an inhalation model with C3HeB/FeJ mice and compared to control mice exposed to saline and unexposed sentinels (all, n=3-19). Inhalation studies were performed using all BDGs ±heat-inactivation (1-hr. autoclave) given BDG solubility increases after heat-inactivation. Outcomes included bronchoalveolar lavage (BAL), differential cell counts (macrophages, neutrophils, lymphocytes, and eosinophils), BALF cytokine and serum IgE and IgG2a expression (by multiplex immunoassay and ELISA). Lastly,ex vivocultured left lung cells were BDG stimulated, and cytokines (multiplex) compared to unstimulated cells. Right lung histology was performed.ResultsWhile each BDG affected lung inflammatory outcomes, pustulan exposure led to the most pro-inflammatory profile of all BDGs tested, including increased inflammatory infiltrate into BAL, increased serum IgE and IgG2a and increased cytokine production. Secondary stimulation of sensitized lung cells by lipopolysaccharide (LPS) significantly increased cytokine expression. Lung histology revealed significant fibrosis in lungs exposed to soluble BDGs pustulan and scleroglucan.ConclusionInhalation of BDGs with distinct branching patterns exhibited varying inflammatory potency and immunogenicity, which lichen-derived pustulan having the greatest effect. Glucan source and solubility should be considered in exposure and toxicological studies.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3