Activation of the inflammatory response of neutrophils by Tamm-Horsfall glycoprotein

Abstract

The activation of human polymorphonuclear leukocytes (PMN) by particulate Tamm-Horsfall glycoprotein (THG) represents an interaction hitherto unrecognized. The potential pathophysiological effect of this phenomenon within the interstitium of the kidney is highlighted by the activation of the respiratory burst, as well as by comprehensive PMN degranulation. Products of the interaction are expressed in terms of phagocytosis, luminol-dependent chemiluminescence, granule marker enzyme release and arachidonic acid metabolism. Significant quantities of the primary, secondary and tertiary granule markers, myeloperoxidase, vitamin B12 binding protein and N-acetyl-beta-D-glucosaminidase, respectively, were secreted in a dose and time-dependent manner. Phagocytosis of the glycoprotein was accompanied by the generation of significant quantities of leukotriene B4. Furthermore, the ability of such a particulate ligand to activate the alternative pathway of complement clearly represents a capacity to augment the inflammatory response. Should the interaction of THG with PMN take place within the interstitium of the kidney, augmented by the deposition of complement proteins on the surface of insoluble aggregates, the resulting inflammatory response may lead to marked tissue damage and eventually result in interstitial fibrosis.

Polarized Expression of Tamm-Horsfall Protein by Renal Tubular Epithelial Cells Activates Human Granulocytes

“…There is evidence that THP may alter the immune response of the host in urinary tract infections since it was shown to induce tumor necrosis factor alpha expression in monocytes (22) and leukotriene B4 and superoxide and gelatinase release in human mononuclear phagocytes (7,25). Therefore, the polarized expression of THP may have an impact on the interaction of tubular epithelial cells with monocytes and/or granulocytes in inflammatory kidney diseases.…”

Role of Tamm-Horsfall protein in the binding and in vivo phagocytosis of type 1 fimbriated Escherichia coli by mouse peritoneal macrophages

“…Horton et al (23) suggested that THP may stimulate phagocytosis since in aggregated form and at high concentrations (>500 µg THP/ml) it increased neutrophil phagocytosis and lysosome degranulation. However, these high concentrations exceed the physiological levels of THP in urine (20-200 µg/ml) and contradict results obtained by Reinhart et al (24), who observed a decrease in the respiratory burst of PMNL after the ingestion of E. coli F1 + bound to THP.…”

Sisters in arms: myeloid and tubular epithelial cells shape renal innate immunity

“…Initially, THP was shown to have anti-inflammatory properties, by suppressing T cells in vitro (93) and binding renal cytokines and lymphokines (IL-1 and TNF) (50). However, a number of subsequent studies also performed in vitro suggested a proinflammatory role of THP, specifically in activating neutrophils (53,67,139) and monocytes (130,144). In addition, Saemann and colleagues (115) demonstrated that THP activates myeloid dendritic cells via TLR4 to acquire a fully mature phenotype.…”