3.4.3 Neutrophils
Neutrophil recruitment is important in the pathogenesis of allergic sensitisation and inflammation.92 Trx1 has an obvious inhibitory effect on the adhesion of neutrophils to vascular endothelial cells. Indeed, Nakamura et al. found that Trx1 can inhibit the adhesion of neutrophils to endothelial cells in a mouse air sac chemotactic model.93 CD62L is an important adhesion molecule that is expressed and shed by neutrophils; it plays a key chemotactic role in the processes of neutrophil adherence to vascular endothelium and blood vessel penetration.94Specifically, exogenous Trx1 acts directly on neutrophils, inhibiting the activation of the p38 mitogen-activated protein kinase (MAPK) signalling pathway, which causes down-regulation of CD62L in neutrophils, and ultimately reduces the adhesion of CD62L to endothelial cells. We previously explained the specific mechanism of its action.95 In addition, C32S/C35S mutant Trx1, with a mutation of the redox function site, cannot inhibit neutrophil adhesion to human umbilical vein endothelial cells, indicating that the redox site of Trx1 is necessary for inhibition of neutrophil adhesion.93 Moreover, in an LPS-induced bronchial inflammation rat model intravenously injected with 8 mg/kg of Trx1 every day, neutrophil infiltration into the bronchial and lung tissues was significantly reduced.96 Although adhesion molecules, such as ICAM-1, expressed by endothelial cells are known to play important roles in neutrophil extravasation, Trx1 does not alter the expression of such adhesion molecules in these cells.93,96 Therefore, Trx1 can inhibit the neutrophil recruitment caused by other chemokines, and it may play a unique role in neutrophil exudation of allergic inflammation.