ESCHERICHIA-COLI MACROPHAGE INTERACTIONS MODULATE MESANGIAL CELL-PROLIFERATION AND MATRIX SYNTHESIS

Patients with chronic renal interstitital diseases often develop glome rular lesions (focal segmental glomerular sclerosis). Because mesangia l expansion (enhanced mesangial cell (MC) growth and matrix accumulati on) has been demonstrated to precede the development of focal segmenta l glomerulosclerosis, we studied the effect of the interaction between bacteria such as Escherichia coli and macrophages on MC proliferation and matrix synthesis, We determined the effect of control media (CM), E. coli supernatant (ESP), serum-free macrophage supernatant (MSP), a nd E. coli-treated macrophage supernatants (HE101-MSP, H10-MSP) on the proliferation of MCs and synthesis of laminin (a component of mesangi al matrix). ESP did not alter MC growth, whereas E. coli MSP increased the mean MC number by 5- to 6-fold when compared to cells treated wit h CM. Both HB101-MSP and H10-MSP stimulated greater (p < 0.05) incorpo ration of [H-3]thymidine when compared with MSP (HB101-MSP 3.1 +/- 0.4 , H10-MSP 2.7 +/- 0.3 vs. MSP 1.6 +/- 0.2 x 10(6) cpm/mu g protein). W hen MC proliferation was judged by incorporation of bromodeoxyuridine, both HE 101-MSP- and H10-MSP-treated cells showed a greater (p < 0.01 ) number of proliferating cells compared with cells treated with eithe r MSP or CM. MC treated with H10-MSP grew in a specific pattern and sh owed a tendency to form hillocks (foci of cell proliferation and matri x aggregation), Both HB101-MSP and H10-MSP enhanced (p < 0.01) synthes is of laminin compared with CM, HB101-MSP-induced enhanced laminin syn thesis was attenuated when MCs were treated with anti-transforming gro wth factor (TGF)-beta antibodies, HB101-MSP also increased mRNA expres sion of TGF-beta by MCs. These results indicate that E. coli-macrophag e interaction has the potential to cause mesangial expansion.