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Neutrophil adherence and transmigration through endothelial cells is enhanced by physiological and therapeutic iron complexes

The role of iron in polymorphonuclear cell (PMN, neutrophil) endothelial cell interactions has scarcely been studied. In innate immunity this is one of the key interactions in fighting and clearing out an invading pathogen. As non-transferrin bound iron (NTBI) has been detected in various patient groups, including end-stage renal disease patients, and even in healthy humans, we questioned whether NTBI could be contributing to neutrophil recruitment to the endothelium. 10µmol/L Fe(III)citrate incubation on endothelial cells for 18 hours, increased the adherence of both treated and non-treated PMN. The increased neutrophil recruitment did not proceed via the classic CD11b/CD18 and ICAM-1 interactions, instead we noted enhancement of the pro-adhesive P-selectin on HUVECs after iron incubation.

Furthermore, increased amount of lactoferrin on the phagocyte membrane was noted on iron-treated PMN. Iron dextran incubation on PMN significantly enhanced transendothelial migration at concentrations of as low as 25µg/mL, without significant enhancement of PECAM-1 expression. However, there is no different in the level of transmigration of untreated PMN through endothelial cells which had been incubated with concentrations of up to 100µg/mL iron dextran, compared to controls. In addition, iron sacharate did not enhance neutrophil transmigration, in the same way as iron dextran, although from both iron preparations, NTBI concentrations of up to 6 µmol/L were measured. In conclusion, this study reports the enhanced adhesion and transmigration of PMN trough an endothelial monolayer. Pharmacological forms of iron given in end-stage renal disease patients on dialysis could modulate the degree of PMN recruitment in inflammation.

Conclusion: This finding implicates that iron is a modulator of innate immune activation.

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Joannes MARX, (Professor)
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