Of odsh were increased 1148 0084 au though not

of ODSH were increased (1.148 ± 0.084 AU), though
not significantly. e NO level in the mice treated with
8.3 mg/kg i.p. of ODSH was significantly lower than WT
mice treated with saline (0.934 ± 0.071 of ODSH low
dose group versus 1.280 ± 0.060 of WT control, p < 0.05),
whereas the NO levels in mice treated with 25 mg/kg
i.p. of ODSH was comparable to WT mice treated with
saline (1.148 ± 0.084 AU of ODSH high dose versus
1.280 ± 0.060 AU of WT control). (Fig. 3 B). ese results
suggest ODSH not only partially restores the decreased
NO secretion following PA infection in CF mice but it
may also a ff ect additional mechanisms to restore the bac-
terial clearance in the lungs of the CF mice.
Alveolar macrophages from CF mice have a greater
impairment in phagocytosis than macrophages derived
from bone marrow
Previous studies have reported a deficit in the clearance of
invading bacterial pathogens, such as PA, in the lungs of
CF patients (Darling and Evans 2003 ; Langan et al. 2015 ).
To determine whether CFTR deficiency impaired mac-
rophage function, we determined the phagocytic activity
of macrophages from CFTR deficient mice. Both bone
marrow-derived macrophages (BMDM) (43.34 ± 5.58%,
p < 0.05) and alveolar macrophages (AM) (21.56 ± 1.98%,
p < 0.0001) harvested from CF mice had a significantly
lower phagocytic activity, compared to the BMDM con-
trol (100.0 ± 19.41%) and AMs (94.20 ± 6.171%) from
WT mice (Figs. 4 A and B). e magnitude of phagocy-
tosis impairment in AM and BMDM was expressed as
percentage change and the impairment of AMs in the
CF mice was greater than that of CF BMDM (phagocy-
tosis impairment as 78.44 ± 1.985% vs 56.66 ± 5.584%,
p < 0.05) (Fig. 4 C). ese results suggest that although
CFTR deficiency can directly impair phagocytic activ-
ity, this e ff ect can be further exacerbated by the airway
microenvironment.
ODSH decreases the airway levels of HMGB1 in PA-infected
CF mice
Previous studies in our lab have shown that the exces-
sive accumulation of HMGB1 in airways of CF patients
A
B
0 0 8.3 25
0
2
4
6
8
ODSH (mg/kg)
Log CFUs/mL of BAL
CF WT
0 0 8.3 25
0
2
4
6
8
ODSH (mg/kg)
Log CFUs/mL of Lungs
CF WT
Fig. 2 ODSH improves bacterial clearance in BALF and lung tissues of CF mice. C57BL/6 mice (WT) and CFTR
- / -
mice (CF) were intratracheally
inoculated with Pseudomonas aeruginosa (PA) at T = 0 and were randomized to receive via i.p. administration of saline or ODSH at 8.3 or 25 mg/kg
at T = 0 and 12 h. A Bronchoalveolar lavage fluid (BALF) and B lung homogenate were harvested 18 h after infection (T = 18 h) and were analyzed
for the amount of viable bacteria by plating serial dilutions of BALF samples followed by colony assay. Bacterial load in the samples is expressed
as log CFUs/mL in BALF or lungs. Data represent the mean ± SEM of four independent experiments (n = 10–14). One-way ANOVA was used for
multiple group comparison to determine statistical significance between control CF group and other groups

Page 8 of 17
Wang et al. Mol Med (2021) 27:79
impairs bacterial clearance in mice with PA lung infec-
tions (Entezari et al. 2012 ). Similarly, the results of this
study indicated an excessive accumulation of airway
HMGB1 in CF mice compared to WT mice (Fig. 5 ). We
therefore determined if the i.p. administration of ODSH
alters HMGB1 accumulation in airways of CF mice. As
shown in Fig.