INVOLVEMENT OF IP-10 IN LUNG INFLAMMATION IN MRL/LPR MICE

Abstract

MRL/Mp-lpr/ lpr (MRL/lpr) mice spontaneously develop systemic lupus erythematosus (SLE) -like disease. The natural history of the pulmonary involvement and the underlying mechanism of leukocyte infiltration into the lungs of MRL/lpr mice and SLE patients remains to be elucidated. The aim of this study was to investigate the expression profiles of chemokine and the chemokine receptor in the lung of the SLE-prone mouse. The expression of IP-10 and its receptor, CXCR3, were evaluated by immunohistology, reverse transcription polymerase chain reaction (RT-PCR), Southern blot analyses and flow cytometer. We used M RL/Mp-+/+ (MRL/+) mice without Fas gene abnormality and C57BL/6 (B6) mice as the control. Lung infiltration and inflammation in MRL/ lpr mice progressed according to monthly increase in age. There was a significant increase in mononuclear cell infiltration into the lung perivascular, peribronchial lesions. Using RT-PCR techniques, the expression of IP-10 mRNA was greater in lungs of MRL/ Ipr mice after 4 months of age than in those of MRL/+ and B6. Macrophage-like cells are likely important sources of IP-10 determined by immunohistology. Furthermore, flow cytometric analyses as well as immunohistology revealed expressed CXCR3 increased infiltrating CD4 positive T lymphocytes in 4 and 6 months of age. Expressed CXCR3 also increased infiltrating CD8 positive T lymphocytes in 4 and 6 months of age. Our present results suggest that IP-10 expression in the lung likely plays a crucial role in lung inflammation associated with Thl cells through CXCR3.