Estradiol and ERβ are more effective than ERα in conferring protection against T/HS induced lung injury.

<p>A) T/HS-induced lung injury, as represented by the percentage of EBD leak within the BALF or B) by the BALF/plasma protein ratio, was increased in the ovariectomized rats and reduced by the administration of estradiol of the estrogen receptor agonists. Data expressed as mean ± SD with 6–8 rats per group. *p<0.01 vs all other groups except the ERα T/HS group. #p<0.01 vs ERα T/SS group. C) T/HS increased the degree of lung neutrophil sequestration, as reflected in MPO levels, in the OVX rats and this was abrogated by the administration of E2 and the ERβ but not the ERα agonist. *p<0.05 vs all other groups.</p

Estradiol and both estrogen receptor agonists ERα and ERβ are protective against T/HS induced gut injury.

<p>A) The extent of villus injury 3 hours after T/HS was reduced back to the levels observed in the PE females by all three estrogen-based therapies. A minimum of 200 villi per animal was counted with 6–8 animals per group. *p<0.001 vs all other T/HS groups, #p<0.05 vs all T/HS groups. B) The incidence of bacterial translocation was increased only in the OVX group subjected to T/HS. *p<0.01 vs all other groups with 6–8 animals per group.</p

iNOS response is abrogated by both E2 and ERβ.

<p>A) The number of iNOS positive enterocytes was increased in all of the T/HS groups but was highest in the OVX rats and the OVX rats receiving the ERα agonist. Data expressed as mean ± SD with a minimum of 100 villi counted per animal with 6–8 animals per group. * p<0.01 vs all other groups, **p<0.01 vs all other groups, and #p<0.05 vs T/HS groups. B) Representative immunohistochemistry micrographs showing iNOS staining of enterocytes.</p

TLR4 deficiency reduces T/HS lymph induced pulmonary iNOS protein levels.

<p>A) and B) Western blot of iNOS in lung WCEs of WT and TLR4^mut mice infused with porcine T/SS and T/HS lymph for 3 hr. B) Densitometry was performed to quantify iNOS and total p42/p44 MAPK expression. Data expressed as mean ± SE (n = 4–7 mice/group).</p

TRIF and Myd88 deficiency confer full and partial protection against T/HS lymph induced microvascular permeability.

<p>A) WT and Myd88^−/− and B) WT and TRIF^mut mice were infused with porcine T/SS and T/HS lymph for 3 hr and lung permeability to EBD was performed. Data expressed as mean ± SE (n = 5–8 mice/ group).</p

TLR2 does not mediate T/HS lymph-induced lung injury.

<p>WT and TLR2^−/− mice infused with porcine T/HS and T/SS lymph for 3 hr. A) Lung permeability to EBD was performed. Data expressed as mean ± SE (n = 4–6 mice/ group). B) MPO levels (U/g) were measured in lung homogenates. Data expressed as mean ± SE (n = 5–6 mice/group).</p