No abstract

Tissue factor (TF) is a transmembrane protein, which is essential for initiation of the coagulation cascade. TF has been reported to play an important role in the progression of endotoxin (lipopolysaccharide, LPS)-mediated endotoxemia, being induced in numerous tissues, such as kidney, spleen and lung. We developed and validated a rabbit anti-murine TF peptide antiserum to localize TF protein in a murine sepsis model. TF protein distribution was compared to localization of TF mRNA and fibrin deposits, the ultimate resultant of procoagulant TF activity. Evident LPS mediated TF mRNA induction was observed in the tubular area at the cortico-medullar junction in the kidney, and TF activity was increased after 6 hours of endotoxemia. In the spleen, however, TF mRNA was induced in the interfollicular region upon LPS injection, corresponding to increased TF protein in the same area. The clusters of TF-protein positive cells in the spleen are predominantly granulocytes, but no TF mRNA expression was observed within these cells. Based on these observations and the presence of TF-protein positive granulocytes after splenectomy, we hypothesize that granulocytes take-up TF for transport to other locations in order to initiate fibrin formation or to induce pro-inflammatory gene expression upon interaction with factor VIIa.

SUMMARY Although parasitic infections do not usually present with disturbance in renal function, glomerular lesions can be seen in most of these infections. The glomerular lesions observed in parasitic infections cover the whole range of glomerular lesions known, but most of them are proliferative. Little is known of the exact pathogenic mechanisms. In this review, we try to explain the glomerular lesions associated with parasitic infections in terms of the specific immunologic events observed during these diseases against the background of recent developments in the general knowledge of the pathogenesis of glomerular disease.

T-cells have been implicated in autoimmune renal injury. To examine the role of T-cells in lupus nephritis we propagated T-cell clones from the cortical interstitium of MRL/lpr mice. All isolated kidney-infiltrating (KI) T-cell clones [6] express surface markers identical to the T-cells regulated by the lpr gene (Thy 1.2+, TCR alpha/beta +, Lyt-2-, L3T4-, B220+). Although KI T-cell clones have the same surface markers as lymph node-infiltrating (LNI) T-cells, they differ functionally. KI T-cells, but not LNI T-cells, are autoreactive and kidney-specific, exclusively proliferating to renal tubular epithelial (TEC) and mesangial cells. In addition, unlike LNI T-cell supernatants (SN), KI T-cell clones SN induce class II and ICAM-1 on cultured TEC. When KI T-cell clones are injected under the renal capsule, class II is increased on TEC. All clones transcribe mRNA for cytokines capable of inducing class II and ICAM-1 (IL-4, TNF-alpha, IFN-gamma). Anti-IFN-gamma mAb prevents the induction of class II and ICAM-1 on cultured TEC. Since class II and ICAM-1 expression on TEC precedes renal injury, the ability to propagate autoreactive, kidney-specific T-cell clones that induce these molecules provides evidence for their role in initiating renal injury in MRL/lpr mice.