ATP release and autocrine signaling through P2X4 receptors regulate γδ T cell activation.

Purinergic signaling plays a key role in a variety of physiological functions, including regulation of immune responses. Conventional αβ T cells release ATP upon TCR cross-linking; ATP binds to purinergic receptors expressed by these cells and triggers T cell activation in an autocrine and paracrine manner. Here, we studied whether similar purinergic signaling pathways also operate in the "unconventional" γδ T lymphocytes.

A3 adenosine receptor inhibition improves the efficacy of hypertonic saline resuscitation.

We reported previously that hypertonic saline (HS) treatment can prevent or upregulate the function of polymorphonuclear neutrophils (PMNs) via A2a-type adenosine receptors or A3-type adenosine receptors (A3R), respectively. A3R translocate to the cell surface upon PMN stimulation, and thus, HS promotes PMN responses under conditions of delayed HS treatment. Here we investigated if inhibition of A3R improves the protective effects of HS resuscitation in a mouse sepsis model.

Hypertonic saline increases gammadeltaT cell-mediated killing of activated neutrophils.

Objective: Hypertonic saline fluids used to resuscitate trauma patients can prevent neutrophil-mediated lung tissue damage, making them attractive alternatives to conventional resuscitation fluids. We have previously shown that gammadeltaT cells, a small T lymphocyte subset, reduce acute inflammatory lung damage by eliminating activated neutrophils that express heat shock protein 72 on the cell surface. Here, we studied whether these protective effects of hypertonic saline are related to improved gammadeltaT cell-mediated neutrophil killing.

Hypertonic saline up-regulates A3 adenosine receptor expression of activated neutrophils and increases acute lung injury after sepsis.

Objective: Hypertonic saline resuscitation reduces tissue damage by inhibiting polymorphonuclear neutrophils. Hypertonic saline triggers polymorphonuclear neutrophils to release adenosine triphosphate that is converted to adenosine, inhibiting polymorphonuclear neutrophils through A2a adenosine receptors. Polymorphonuclear neutrophils also express A3 adenosine receptors that enhance polymorphonuclear neutrophil functions.

Roles of heat shock proteins and gamma delta T cells in inflammation.

Elimination of activated inflammatory cells that infiltrate and damage host organs can reduce morbidity and mortality. A better understanding of the mechanisms by which these processes occur may lead to new approaches to prevent tissue damage. The lungs, gastrointestinal tract, and skin are particularly prone to infection and collateral damage by inflammatory cells.

A3 and P2Y2 receptors control the recruitment of neutrophils to the lungs in a mouse model of sepsis.

We have recently shown that A3 adenosine receptors and P2Y2 purinergic receptors play an important role in neutrophil chemotaxis. Chemotaxis of neutrophils to sites of infections is critical for immune defense. However, excessive accumulation of neutrophils in the lungs can cause acute lung tissue damage.

Heparanase pretreatment attenuates endotoxin-induced acute lung injury in rats.

A central event of systemic inflammation and septic organ injury is infiltration of tissues with polymorphonuclear neutrophils, likely modulated by the integrity of the extracellular matrix underlying the vascular endothelium. In the present study, the effect of matrix-modifying endoglycosidase (heparanase) on endotoxin (LPS)-induced inflammatory lung injury was investigated in rats. Animals were treated with heparanase or LPS or pretreated with heparanase before LPS injection, and acute lung injury was verified histologically and characterized by analysis of bronchoalveolar lavage fluids.

Ultrastructural features of lymphocyte suppression induced by anthrax lethal toxin and treated with chloroquine.

Antibacterial therapy does not fully protect against anthrax because of severe systemic intoxication. Lysosomal processing of anthrax lethal toxin (LTX) is a key event in the disease pathogenesis, and agents interfering with this process, like chloroquine (CQ), may have practical applications. Although LTX is known to induce T-cell suppression, precise mechanisms of this phenomenon are not completely characterized.

Chloroquine prevents T lymphocyte suppression induced by anthrax lethal toxin.

Lysosomal processing of lethal toxin (LTX) is a key event in the pathogenesis of anthrax. This study investigated the ability of chloroquine (CQ) to interfere with this processing and thereby to reduce suppression of T lymphocytes. T lymphocytes isolated from blood were activated, by cross-linking of CD3, in both the absence and presence of LTX and CQ and then were assayed by flow cytometry and immunoblotting.

Surface expression of HSP72 by LPS-stimulated neutrophils facilitates gammadeltaT cell-mediated killing.

During inflammation and sepsis, accumulation of activated neutrophils causes lung tissue damage and organ failure. Effective clearance of neutrophils reduces the risk of organ failure; however, its mechanisms are poorly understood. Because lungs are rich in gammadeltaT cells, we investigated the physiological role of these cells in the protection of lung tissue from infiltrating neutrophils.