The Long Pentraxin Ptx3 Is Synthesized in IgA Glomerulonephritis and Activates Mesangial Cells

Abstract

The long pentraxin PTX3 has been recently involved in amplification of the inflammatory reactions and regulation of innate immunity. In the present study we evaluated the expression and role of PTX3 in glomerular inflammation. PTX3 expression was investigated in the IgA, type I membranoproliferative, and diffuse proliferative lupus glomerulonephritis, which are characterized by inflammatory and proliferative lesions mainly driven by resident mesangial cells, and in the membranous glomerulonephritis and the focal segmental glomerular sclerosis, where signs of glomerular inflammation are usually absent. We found an intense staining for PTX3 in the expanded mesangial areas of renal biopsies obtained from patients with IgA glomerulonephritis. The pattern of staining was on glomerular mesangial and endothelial cells. Scattered PTX3-positive cells were also detected in glomeruli of type I membranoproliferative glomerulonephritis. The concomitant expression of CD14 suggests an inflammatory origin of these cells. Normal renal tissue and biopsies from patients with the other glomerular nephropathies studied were mainly negative for PTX3 expression in glomeruli. However, PTX3-positive cells were detected in the interstitium of nephropathies showing inflammatory interstitial injury. In vitro, cultured human mesangial cells synthesized PTX3 when stimulated with TNF-α and IgA and exhibited specific binding for recombinant PTX3. Moreover, stimulation with exogenous PTX3 promoted mesangial cell contraction and synthesis of the proinflammatory lipid mediator platelet-activating factor. In conclusion, we provide the first evidence that mesangial cells may both produce and be a target for PTX3. The detection of this long pentraxin in the renal tissue of patients with glomerulonephritis suggests its potential role in the modulation of glomerular and tubular injury.

Binding of the Long Pentraxin PTX3 to Factor H: Interacting Domains and Function in the Regulation of Complement Activation

“…It has been reported that renal mesangial and epithelial cells produce PTX3 (61,62). It is possible to hypothesize that a mechanism involving a disturbed interaction of locally produced PTX3 with FH could be involved in the pathogenesis of this condition.…”

The Pathogenesis of Lupus Nephritis

“…For example, renal cells produce pentraxin-3, which has the potential to directly inhibit leukocyte recruitment by interfering with P-selectin on the surface of activated endothelial cells. 68,69 In lupuslike autoimmunity of C57BL/6 lpr/lpr mice, the role of pentraxin-3 seems to be organ specific, because it suppresses lymphocyte recruitment to the lungs but not to the kidney. 70 Infiltrating leukocytes form de novo perivascular tertiary lymphoid organs inside the kidney, which involve the clonal expansion and ongoing somatic hypermutation of B cells in proximity to T cell aggregates.…”

Plasma Pentraxin 3 in Patients with Chronic Kidney Disease

“…The production of PTX3 in human renal epithelial cells was recently reported (22), together with an increased PTX3 expression in mesangial cells of renal biopsies obtained from patients with IgA glomerulonephritis (23), suggesting a role in the innate immune response and inflammatory reactions in the kidney. The bigger molecular size for PTX3 (40.6 kD) compared with CRP (21.5 kD) may suggest increased retention in uremia.…”