FIGURE 6.

The extracellular nicotinamide phosphoribosyltransferase (NAMPT)-neutralising ALT-100 monoclonal antibody (mAb) attenuates mitogen-activated protein (MAP) kinase signalling in “one-hit” and “two-hit” pre-clinical acute respiratory distress syndrome (ARDS)/ventilator-induced lung injury (VILI) models. a) Lung tissue homogenates from one-hit lipopolysaccharide (LPS)-exposed (1 mg·kg⁻¹, 18 h) and two-hit LPS/VILI-exposed (LPS 22 h; mechanical ventilation 4 h, tidal volume 20 mL·kg⁻¹) C57B6 wild-type mice were probed for phospho-proteins and total β-actin (Western blot). LPS- and LPS/VILI-challenged mice displayed robust NFκB and MAP kinase phosphorylation (pp-p38, pp-JNK, pp-42/44 extracellular signal regulating kinase (ERK)) as evidence of pathway activation. b) Treatment with the eNAMPT-neutralising ALT-100 mAb (0.4 mg·kg⁻¹, at time 0 h) resulted in significant reductions in both NFκB and MAP kinase pathway activation in the one-hit- and two-hit-exposed mice captured by densitometric measurements (n=3). DU: densitometric units. *: p<0.05.