Surface antigens of human mesangial cells: impact of growth surface or IL‐1α

Abstract

The interactions of mesangial cells (MC) with their environment are important events in glomerular physiology and pathology, yet a detailed characterization of the MC-surface antigens mediating these interactions is still lacking. In this study, a comparative phenotype analysis of primary human MC in culture using 191 monoclonal antibodies directed against 108 antigens was performed by flow-cytometry. The MC were grown on three different surfaces (human matrix, fibronectin, polystyrene) and cultured in the presence or absence of IL-1alpha. Seventy-one antibodies recognizing 35 different antigens (integrins: CD29, 49b, 49c, 49e, 51, 61; immunoglobulin gene family: CD54, 58, 90, 106, 146, 147, 166; growth factor receptors: CD105, 140b; apoptosis related: CD95; hemostatis related: CD141, 142; miscellaneous: CD44, 109, 138, 151, 157, 165, and 11 nonclustered antigens) reacted with mesangial cells. CD58, 109, 146, 147, 151, 157, 165, and 166 are reported for the first time to be present on human mesangial cells. In comparison to growth on polystyrene, CD44, 54, 95, 105, 109, 140b, 146, 147, 157, 165 and 166, were up-regulated on fibronectin, and CD44, 54, 90, 95, 105, 106, 109, 138, 140b, 141, 142, 146, 147, 151, 157, 165 and 166 were up-regulated on human matrix. The stimulation by IL-1alpha up-regulated CD44, 49e, 51, 54, 61, 106 on MC on polystyrene; CD49e, 51, 61, 106, 146, 165 on MC on fibronectin, and CD49e, 51, 54 on MC grown on human matrix. This analysis of surface antigen expression provides new information to enable a better understanding of the role of mesangial cells in glomerular pathophysiology.

Thy-1, a versatile modulator of signaling affecting cellular adhesion, proliferation, survival, and cytokine/growth factor responses

“…However, more recent studies have determined that anti-Thy-1-induced nephritis is a combination of complement-mediated necrosis and apoptosis [35]. As Thy-1 is also expressed on human mesangial cells [74], understanding the role of Thy-1 in inducing mesangial cell death in mice may have implications in the understanding of the pathogenesis and treatment of renal diseases in humans. To date, changes in expression of Thy-1 in human renal disease have not been reported.…”

Immunoliposome Targeting to Mesangial Cells

“…In addition, mesangial cells have a high natural capacity of phagocytosis that, when combined with good accessibility, facilitate the accumulation of encapsulated drugs into the cytoplasm. Sengoelge et al (26) described a high expression of the Thy1.1 antigen on the human mesangial cell surface, in conjunction with a multitude of other gene products. Thus, in addition to the Thy1.1 antigen, other antigens may be evaluated for the directed targeting of therapeutic agents to mesangial cells to treat human glomerulonephritis.…”

Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules

“…59 By comparison, immunoliposomes containing the Thy1.1 antibody had significant superiority over the HVJ-liposome in mediating gene transfers to the MCs in both in vitro and in vivo experiments. 15,16 The translational potential of the anti-Thy1.1 liposome to human renal disease treatment may be problematic 36,65 because Hartner et al, 66 in a study that compared MC surface α8 integrin and Thy1.1 antigen levels, concluded that α8 integrin is more specifically expressed in human MCs relative to glomerular endothelial and epithelial cells. Anti-α8 integrin-modified immunoliposomes have been shown to target therapeutic cargoes to the glomerular mesangium and the mesangial cytoplasm in normal mice and glomerulonephritis mice.…”

“…While the data have been promising, they also highlighted many uncertainties, the chief of which is that most of the systems in their current forms could not be directly applied to treat human kidney diseases. 13,36,65 Future research will need to address the important knowledge and technology gaps relating to the cytotoxicity of the NPs on healthy glomerular cells, the impact of long-term chronic exposure of the kidney and other organs to the NPs, the molecular mechanisms of actions and related toxicodynamics underlying the adverse effects of the NPs.…”