Exposure to Particulate 1→3-β-Glucans Induces Greater Pulmonary Toxicity Than Soluble 1→3-β-Glucans in Rats

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Abstract
1 M 3- g -Glucans, derived from the inner cell wall of yeasts and fungi, are commonly found in indoor air dust samples and have been implicated in organic dust toxic syndrome. In a previous study, it was reported that 1 M 3- g -glucan (zymosan A) induced acute pulmonary inflammation in rats. This study investigates which form of 1 M 3- g -glucans, particulate or soluble, is more potent in inducing pulmonary inflammation. Zymosan A was suspended in 0.25 N NaOH for 30 min, neutralized, dialyzed for 2 d using deionized water, and particulate and soluble fractions were collected. Male Sprague-Dawley rats were exposed via intratracheal instillation to NaOH-soluble or NaOH-insoluble zymosan A. At 18 h postexposure, various indicators of pulmonary response were monitored, including indicators of lung damage, such as serum albumin concentration and lactate dehydrogenase (LDH) activity in acellular bronchoalveolar lavage fluid. Inflammation was characterized by an increase in lavageable polymorphonuclear leukocytes (PMN). Pulmonary irritation (breathing frequency increase) and oxidant production (nitric oxide and chemiluminescence, CL) were also monitored. Exposure to the particulate form of NaOH-treated zymosan produced a significant increase in all these indicators. In contrast, rats exposed to the NaOH-soluble fraction were not markedly affected except for LDH, PMN, and CL. However, these increases were significantly less than with exposure to NaOH-insoluble zymosan. Therefore, results demonstrate that particulate zymosan A is more potent in inducing pulmonary inflammation and damage in rats than the soluble form of this g -glucan.