INTERSTITIAL MYOFIBROBLASTS IN EXPERIMENTAL RENAL INFECTION AND SCARRING

We have examined the temporal and spatial distribution of myofibroblas t-like cells, a phenotype with fibroblast and smooth muscle features, in an experimental model of renal infection. Escherichia coli organism s (10(5)) were inoculated directly into the renal cortex of Sprague-Da wley rats weighing 270 g. Saline was substituted in a control group. T he animals were sacrificed at five time points up to day 24 (E. coli n = 8, controls n = 3 each interval). Myofibroblasts were identified by morphology and immunohistochemistry for alpha smooth muscle actin (al pha-SMA) and compared with staining for monocytes (ED-1), collagen III , and bromodeoxyuridine incorporation. Histological changes included a focal lesion in E. coli infected animals. Interstitial alpha-SMA stai ning was confined to spindle-shaped cells resembling myofibroblasts. T he percent fractional area of alpha-SMA staining in the lesion increas ed from 0.12 +/- 0.09 at day 1 to 20.0 +/- 7.1 at day 3 (p < 0.005), d ecreasing progressively to 2.0 +/- 2.6 by day 24. This paralleled brom odeoxyuridine incorporation in myofibroblasts: 0.4 +/- 0.5 cells/0.25 mm(2) at day 1, 105.0 +/- 36.3 at day 3, and 2.6 +/- 2.2 cells/0.25 mm (2) at day 24. ED-1-positive cells increased from 374 +/- 200/0.25 mm( 2) at day 1 to 894 +/- 88 at day 3 (p < 0.01), declining to 230 +/- 10 8/0.25 mm(2) by day 24. Intracellular collagen III and alpha-SMA stain ings were colocalized at day 3. The fractional area of collagen III in creased by day 24 (p < 0.05). In conclusion, myofibroblasts accumulate transiently during renal interstitial fibrosis and are derived at lea st in part from local proliferation. Double labeling suggests that myo fibroblasts may be synthetically active.