INTRODUCTION: In the nonobese diabetic (NOD) mouse model of Sjögren's syndrome, 
lymphocytic infiltration is preceded by an accumulation of dendritic cells in 
the submandibular glands (SMGs). NOD mice also exhibit an increased frequency of 
mature, fractalkine receptor (CX3C chemokine receptor [CX3CR]1) expressing 
monocytes, which are considered to be precursors for tissue dendritic cells. To 
unravel further the role played by fractalkine-CX3CR1 interactions in the 
salivary gland inflammation, we studied the expression of fractalkine in NOD 
SMGs.
METHODS: We studied protein expression using Western blot analysis of whole 
tissue lysates. Protease activity was measured in salivary gland tissue lysates 
using fluorimetric substrates. Digestive capacity of enzymes was determined by 
in vitro incubation of recombinant enzyme and fractalkine, followed by protein 
staining and Western blot.
RESULTS: Fractalkine was detected in salivary glands of both NOD and control 
mice at all ages. Western blot analysis showed fractalkine cleavage with 
increasing age, which was more pronounced in NOD mice. This cleavage resulted in 
a decrease in the 31 kDa form of the protein, and the generation of an 
approximately 19 kDa band. Furthermore, in NOD animals older than 15 weeks, we 
noted the presence of a unique approximately 17 kDa fragment. This cleavage was 
organ specific, because it did not occur in brain or pancreas. Increased 
gelatinase and alpha-secretase activity were detected in NOD SMG and contributed 
to cleavage of the 31 kDa protein. Because aberrant cleavage products may induce 
autoimmunity, we studied the presence of autoantibodies against fractalkine. 
Indeed, NOD mice exhibited significantly more antibodies against fractalkine 
than did control animals.
CONCLUSION: These data indicate that aberrant proteolytic activity in the NOD 
SMG results in increased fractalkine cleavage and generation of a unique 
fractalkine fragment. This specific cleavage may contribute to autoimmunity.