Co-exposure to zymosan A and heat-inactivated Asian sand dust exacerbates ovalbumin-induced murine lung eosinophilia

Abstract

BackgroundEpidemiological studies have implicated Asian sand dust (ASD) in the increased prevalence of respiratory disorders, including asthma. It has been observed that fungal elements such as β-glucan can be adsorbed onto ASD. In the present study, the exacerbating effect of the combined exposure to zymosan A (ZymA) containing yeast β-glucan and heat-inactivated ASD on ovalbumin (OVA)-induced murine lung eosinophilia was investigated.MethodsBALB/c mice were repeatedly instilled intratracheally with one of eight immunogenic formulations consisting of various combinations of (1) ZymA, (2) ASD that was briefly heated to remove organic substances (H-ASD), and (3) OVA in normal saline, or each of the above alone. Pathologic changes, cytological alterations in bronchoalveolar lavage fluid (BALF), changes in inflammatory cytokines and chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were investigated.ResultsExposure to ZymA with or without OVA had no effect on most indicators of lung inflammation. Exposure to H-ASD with OVA increased the recruitment of inflammatory cells to the lungs and the serum levels of OVA-specific IgE and IgG1. The combination OVA + ZymA + H-ASD induced a marked recruitment of eosinophils and upregulation of T helper 2 (Th2) cytokines (interleukin [IL]-4 and IL-13), IL-6, eotaxin/CCL11, and monocyte chemotactic protein (MCP)-3/CCL7 in BALF and OVA-specific IgE in serum. This treatment also induced the most severe pathological changes in the lungs of mice. ZymA was found to boost the effects of H-ASD, thereby exacerbating the OVA-induced allergic inflammation, even though ZymA alone did not have such effect.ConclusionsThe results suggest that fungal elements such as β-1,3-glucan aggravate the allergic inflammation caused by ASD. Our findings may facilitate prophylaxis of some allergic diseases in Asia.

Mechanisms underlying the health effects of desert sand dust

“…Τhe exacerbating effect of a combined exposure to zymosan A (ZymA; from the yeast Saccharomyces cerevisiae , as a source of β-glucan) and H-ASD (National Institute for Environmental Study No.30 ‘Gobi Kosa Dust’) on OVA-induced murine lung eosinophilia has also been investigated ( Sadakane et al 2016 ). Male BALB/c mice were repeatedly instilled IT with one of eight immunogenic formulations prepared with mixed or individual solutions of (1) ZymA, (2) H-ASD (100 μg), and (3) OVA.…”

Effects of co‐exposure of lipopolysaccharide and β‐glucan (Zymosan A) in exacerbating murine allergic asthma associated with Asian sand dust

“…We hypothesized that co-exposure of LPS and ZymA with H-ASD The co-exposure induced a significant increase in total cell number and production of MCP-1 and MCP-3 and tended to increase Kitaura et al, 1996;Ponath et al, 1996), and MCP-1 and IL-17 facilitate the recruitment of monocytes (Matsushima, Larsen, DuBois, & Oppenheim, 1989) and neutrophils (Laan et al, 1999), respectively, during inflammation. We used the same doses of LPS (1 ng) and ZymA (20 ng) as in previous studies (Ren et al, 2014;Sadakane et al, 2016). The levels of eotaxin, MCP-3 and MCP-1 in BALF were markedly increased in OVA + ZymA + H-ASD treatment compared with the control, ZymA only, OVA-only or OVA + ZymA treatment (IL-17 was not measured) (Sadakane et al, 2016).…”

“…We used the same doses of LPS (1 ng) and ZymA (20 ng) as in previous studies (Ren et al, ; Sadakane et al, ). The levels of eotaxin, MCP‐3 and MCP‐1 in BALF were markedly increased in OVA + ZymA + H‐ASD treatment compared with the control, ZymA only, OVA‐only or OVA + ZymA treatment (IL‐17 was not measured) (Sadakane et al, ). For LPS, the OVA + LPS (1 ng) + H‐ASD treatment tended to increase these chemokines and IL‐17 compared with control, LPS‐only, OVA‐only or OVA + LPS treatment, but the effect was not significant (Ren et al, ).…”

“…in the control group received an intratracheal administration of 0.1 mL of sterile saline. These dosage settings were identical to those employed in our previous studies that verified the co-exposure effects of these ligands (Ren et al, 2014;Sadakane et al, 2016). All mice (age = 14 weeks) were anesthetized by intraperitoneal injections of pentobarbital and then killed by exsanguination one day after the last intratracheal administration.…”

“…Further, in recently published studies, we demonstrated that co‐exposure of lipopolysaccharide (LPS) and H‐ASD exacerbates ovalbumin (OVA)‐induced murine lung eosinophilia (Ren et al, ). These effects included enhancement of recruitment of neutrophils and eosinophils to the lung, and a synergistic increase of T‐helper (Th)2 cytokines as well as co‐exposure of Zymosan A (ZymA, containing β‐glucan), OVA and H‐ASD also enhanced the upregulation of Th2 cytokine levels associated with the exacerbation of murine lung eosinophilia (Sadakane, Ichinose, Nishikawa, Takano, & Shibamoto, ).…”