Red cell ABO incompatibility and production of tumour necrosis factor-alpha

Tumour necrosis factor-alpha (TNF) is a major mediator of diverse pathophysiological events similar to those of haemolytic transfusion reactions (HTR), such as fever, intravascular coagulation and organ failure. However, the possible role of TNF in HTR has not been investigated. We have constructed an in vitro whole blood model of HTR to examine whether TNF may be produced in red cell ABO incompatibility. TNF was observed in plasma, in a dose dependent manner, when ABO incompatible red cells were added, but not with compatible (group O) cells. Plasma TNF levels were maximal at 2 h, and declined to control levels by 24 h. Haemolysis of incompatible red cells was accompanied by TNF production. Immune haemolysis induced TNF gene expression by buffy coat leucocytes, as determined by Northern blot analysis. Heat inactivation of plasma abolished TNF production, whereas prior treatment with interferongamma augmented the response. These results demonstrate that a major cytokine is produced in response to red cell incompatibility, and suggest that TNF may play a role in the pathogenesis of haemolytic transfusion reactions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75627/1/j.1365-2141.1991.tb04485.x.pd

An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells

Here we investigate the dynamics of the hepatic intravascular immune response to a pathogen relevant to invariant natural killer T cells (iNKT cells). Immobilized Kupffer cells with highly ramified extended processes into multiple sinusoids could effectively capture blood-borne, disseminating Borrelia burgdorferi, creating a highly efficient surveillance and filtering system. After ingesting B. burgdorferi, Kupffer cells induced chemokine receptor CXCR3–dependent clustering of iNKT cells. Kupffer cells and iNKT cells formed stable contacts via the antigen-presenting molecule CD1d, which led to iNKT cell activation. An absence of iNKT cells caused B. burgdorferi to leave the blood and enter the joints more effectively. B. burgdorferi that escaped Kupffer cells entered the liver parenchyma and survived despite Ito cell responses. Kupffer cell–iNKT cell interactions induced a key intravascular immune response that diminished the dissemination of B. burgdorferi

CXC chemokine receptor 2 contributes to host defense in murine urinary tract infection

CXC chemokines have been implicated in the recruitment of neutrophils to sites of infection. To determine the role of CXC chemokines in the host response to urinary tract infection (UTI), female mice were treated with an antibody against the major CXC chemokine receptor in the mouse, CXCR2, before intravesical inoculation with Escherichia coli. Anti-CXCR2 prevented the influx of neutrophils in urine and kidneys. The absence of a neutrophil response only temporarily impaired the clearance of bacteria from the urinary tract, as indicated by 100- and 1000-fold more E. coli colony-forming units in urine and kidneys of anti-CXCR2-treated mice at 24 h, but not at 48 h, after the infection. UTI induced increases in the renal concentrations of the CXCR2 ligands macrophage inflammatory protein-2 and KC, which were not influenced by anti-CXCR2 administration. CXC chemokines play an important role in the development of a local inflammatory response to UT