SummaryRenal injury in diabetes mellitus is associated with progressive interstitial fibrosis and extracellular matrix accumulation. However, the phenotypes of cells forming the interstitial infiltrate in diabetic nephropathy have not been precisely defined. There is increasing evidence for the association of mast cells with angiogenesis, chronic inflammatory conditions and fibrosis. We have recently shown that human mast cells can produce the non-fibrillar short chain type VIII collagen in vivo. Using immunohistochemistry, in situ hybridisation and reverse transcriptasepolymerase chain reaction, we examined the contribution of mast cells and type VIII collagen to the fibrotic changes occurring in biopsy-proven diabetic nephropathy. We observed that the number of interstitial mast cells was significantly increased in diabetic nephropathy compared with normal kidney tissue. In specimens from diabetic subjects, intense immunohistochemical staining for type VIII collagen was detected in mast cells, on periglomerular fibres and in perivascular and interstitial sites. The expression of type VIII collagen in periglomerular and interstitial sites coincided with that of alpha smooth muscle actin, a marker for myofibroblastic differentiation, mRNA for type VIII collagen was detected by reverse transcriptase-polymerase chain reaction in diabetic nephropathy and in a human mast cell line. By in situ hybridisation the transcripts for type VIII collagen were localised to renal mast cells. The increased number of mast cells and the elevated type VIII collagen deposition in human diabetic nephropathy provides a potential link between the extracellular matrix accumulation and the fibrosis observed in this condition. [Diabetologia (1996[Diabetologia ( ) 39: 1215[Diabetologia ( -1222

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Type VIII collagen was first detected as a secretion product of diverse endothelial cell cultures, including those derived from aorta, arteries and veins. Initial studies of its tissue distribution (using a monoclonal antibody) showed it to be present in a restricted number of tissues and failed to find it in the vasculature. Recently, type VIII collagen was shown (using monospecific polyclonal antibodies) to be a component of large blood vessels with predominant localization in the subendothelium. We applied an improved immunofluorescence technique using these antibodies to define the tissue distribution of type VIII collagen. We show that it is a component of arterioles and venules in muscle, heart, kidney, spleen, liver and lung and is also found in connective tissue layers around hair follicles, around nerve bundles in muscle, in the dura of the optic nerve, in cornea and sclera, and in the perichondrium of cartilaginous tissues. This collagen variant appears to have a wider distribution than originally assumed. It is a macromolecular component of the subendothelium, possibly a constituent of the vascular intimal basement membrane.

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