Allogeneic activation is attenuated in a model of mouse lung perfused with magnesium-deficient blood.
Hypomagnesemia, which is frequently observed in patients treated with calcineurin inhibitors to prevent rejection after allogeneic transplantation, has been associated with a faster rate of decline in allograft function. The effect of hypomagnesemia on lung allograft has not been reported yet. In our model of isolated mouse lung, we have evaluated the early effects of allogeneic lung perfusion with blood from magnesium (Mg)-deficient mice for 3 h on lung activation and remodelling, compared to isogeneic perfusion. Hypomagnesemia (0.21+/-0.07 mmol Mg(2+)/l) was observed in blood from Mg-deficient mice, but no inflammatory pattern. The mRNA level of the intercellular adhesion molecule (ICAM)-1, but neither of the vascular cell adhesion molecule (VCAM)-1, nor of the cytokines tumor necrosis factor (TNF)alpha and interleukin (IL)-2, was enhanced (p<0.05). Although caspase-3 mRNA was transiently enhanced, no apoptotic cells were evidenced in lung tissues even after 3 h. Using cDNA array, we found that the genes encoding RANKL, RANK, TNFR2, NFATX, IL-1R2, IL-6R gp130, SOCS3, PDGFRB, P63, CSF3R, CXCL1, CXCL5, CX3CL1, CSF1, which are involved in inflammation and apoptosis regulation, were markedly up-regulated in allogeneic conditions. Our results support a limited allogeneic activation and an early stage of the inflammatory process in lung, at the time of inflammatory cell recruitment without lung tissue remodelling, as a result of hypomagnesemia. These findings suggest that cyclosporine-related hypomagnesemia, observed in most of the transplanted patients, does not constitute an additional risk for lung allograft outcome.
Sabbagh
Fadi
F
CNRS UMR 8162, IFR 13, Université Paris-Sud 11, Centre Chirurgical Marie-Lannelongue, 133 avenue de la Résistance, 92350 Le Plessis Robinson, France.
Lecerf
Florence
F
Maurois
Pierre
P
Bac
Pierre
P
German-Fattal
Michèle
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000517:prevention & control; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007249:Inflammation / Q000209:etiology*; D008168:Lung / Q000473:pathology*; D016040:Lung Transplantation / Q000473:pathology; D008275:Magnesium Deficiency / Q000139:chemically induced / Q000150:complications*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger