TLR Cross-Talk Mechanism of Hemorrhagic Shock-Primed Pulmonary Neutrophil Infiltration

ABSTRACT

Hemorrhage resulted from severe trauma renders patients susceptible to the development of acute lung injury (ALI). The accumulation of polymorphonuclear neutrophils (PMN) in the lung is a critical event in the development of ALI. PMN migration is a result of a cascade of cellular events, in which PMN, endothelial cells (EC), and macrophages (M􀀁) act in concert. Recent studies explored interrelated novel findings indicating that Toll-like receptors (TLRs) crosstalk mechanisms occurring in PMN, EC, and MΦ are important determinants for hemorrhage-primed PMN migration. In M􀀁 and EC, LPS acts through TLR4 signaling to up-regulate TLR2. Oxidant signaling derived from hemorrhage-activated PMN NAD(P)H oxidase enhances the TLR2 upregulation through PMN-MΦ or PMN-EC interaction, resulting in an amplified release of cytokines and chemokines from the MΦ and expression of adhesion molecules in the EC in response to TLR2 ligands, thereby promoting PMN migration. This review provides an insight of the mechanisms.

Keywords:

Acute lung injury, endothelial cells, hemorrhagic shock, HMGB1, macrophages, NAD(P)H oxidase, neutrophils, TLR.