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.