Escherichia coli-macrophage interactions modulate mesangial cell proliferation and matrix synthesis

Patients with chronic renal interstitital diseases often develop glomerular lesions (focal segmental glomerular sclerosis). Because mesangial expansion (enhanced mesangial cell (MC) growth and matrix accumulation) has been demonstrated to precede the development of focal segmental 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), and E. coli-treated macrophage supernatants (HB101-MSP, H10-MSP) on the proliferation of MCs and synthesis of laminin (a component of mesangial 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 with CM. Both HB101-MSP and H10-MSP stimulated greater (p < 0.05) incorporation of [3H]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/micrograms protein). When MC proliferation was judged by incorporation of bromodeoxyuridine, both HB101-MSP- and H10-MSP-treated cells showed a greater (p < 0.01) number of proliferating cells compared with cells treated with either MSP or CM. MC treated with H10-MSP grew in a specific pattern and showed a tendency to form hillocks (foci of cell proliferation and matrix aggregation). Both HB101-MSP and H10-MSP enhanced (p < 0.01) synthesis of laminin compared with CM. HB101-MSP-induced enhanced laminin synthesis was attenuated when MCs were treated with anti-transforming growth factor (TGF)-beta antibodies. HB101-MSP also increased mRNA expression of TGF-beta by MCs. These results indicate that E. coli-macrophage interaction has the potential to cause mesangial expansion.