Pattern Recognition Receptor-Dependent Mechanisms of Acute Lung Injury

Abstract

Acute lung injury (ALI) that clinically manifests as acute respiratory distress syndrome is caused by an uncontrolled systemic inflammatory response resulting from clinical events including sepsis, major surgery and trauma. Innate immunity activation plays a central role in the development of ALI. Innate immunity is activated through families of related pattern recognition receptors (PRRs), which recognize conserved microbial motifs or pathogen-associated molecular patterns (PAMPs). Toll-like receptors were the first major family of PRRs discovered in mammals. Recently, NACHT–leucine-rich repeat (LRR) receptors and retinoic acid–inducible gene–like receptors have been added to the list. It is now understood that in addition to recognizing infectious stimuli, both Toll-like receptors and NACHT-LRR receptors can also respond to endogenous molecules released in response to stress, trauma and cell damage. These molecules have been termed damage-associated molecular patterns (DAMPs). It has been clinically observed for a long time that infectious and noninfectious insults initiate inflammation, so confirmation of overlapping receptor-signal pathways of activation between PAMPs and DAMPs is no surprise. This review provides an overview of the PRR-dependent mechanisms of ALI and clinical implication. Modification of PRR pathways is likely to be a logical therapeutic target for ALI/acute respiratory distress syndrome.

TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate

“…Accumulating data in the literature suggest that patternrecognizing receptors play a significant role in acute inflammatory diseases [20,21]. In the present study, we observed that pancreatitis-associated amylase release, neutrophil recruitment and tissue damage were greatly decreased in animals lacking TLR4 whereas animals lacking TLR2 were no different from wild-type animals.…”

Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation

“…Frequently, SIRS leads to dysfunction of multiple organs, including renal failure and acute lung injury. It has become clear that the innate immune system and its PRRs are the main players in the molecular pathway that leads to SIRS associated with trauma [21]. Indeed, it has been shown that several DAMPs, such as HMGB1 and S100 protein, are released into the bloodstream after severe trauma, and these DAMPs have been linked to the development of organ failure after trauma [22,23].…”

Nogo-B Facilitates LPS-Mediated Immune Responses by Up-Regulation of TLR4-Signaling in Macrophage RAW264.7

“…TLRs are abundantly expressed in macrophages and play an important role in Gram-negative sepsis or artificial LPS exposure to trigger the innate immune system [33, 34]. Specifically, TLR4 is essential for the opsonization of LPS, a physiologic membrane-bound component of the outer membrane of Gram-negative bacteria.…”