PTX3 in small-vessel vasculitides: An independent indicator of disease activity produced at sites of inflammation

Fazzini, Fausto; Peri, Giuseppe; Doni, Andrea; Dell’Antonio, Giacomo; Cin, Elena Dal; Bozzolo, Enrica; D'Auria, Francesca; Praderio, Luisa; Ciboddo, Gianfranco; Sabbadini, Maria Grazia; Manfredi, Angelo A.; Mantovani, Alberto; Querini, Patrizia Rovere

doi:10.1002/1529-0131(200112)44:12<2841::aid-art472>3.0.co;2-6

Cited by 248 publications

(211 citation statements)

References 37 publications

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“…In vivo, PTX3 expression has been observed in diseased human vessels during small vessel vasculitis (21) and advanced atherosclerosis (20). In the present study we found intense staining of PTX3 in the mesangium of patients with IgA GN.…”

Section: Discussionsupporting

confidence: 70%

“…An increased level of acute phase proteins and, in particular, of C-reactive protein, has recently been reported in IgA GN (26). Indeed, it has been proposed that PTX3 may play the same function in the periphery as C-reactive protein does in the circulation (12,21). We also found the expression of PTX3 in endothelial cells and in CD14-positive monocytes infiltrating the renal interstitium in IgA GN with tubulo-interstitial injury, indicating that the cells involved in the inflammatory process were activated to synthesize PTX3.…”

Section: Discussionmentioning

confidence: 99%

“…This is supported by studies showing the ability of PTX3 to bind to the C1q component of the complement cascade (12) and to participate in the clearance of apoptotic cells (16). Moreover, PTX3 is elevated in critically ill patients, with a gradient from systemic inflammatory response syndrome to septic shock (17), and in several other diseases, such as myocardial infarction (18), rheumatoid arthritis (19), atherosclerosis (20), and small vessel vasculitis (21).…”

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confidence: 99%

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

Bussolati

Peri

Salvidio

et al. 2003

The Journal of Immunology

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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.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Bussolati

Peri

Salvidio

et al. 2003

The Journal of Immunology

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“…Fazzini [21] and Hollan [19] reported serum PTX3 concentrations (not plasma) of 28 SLE patient and three patients with SLE, respectively. The mean serum PTX3 concentration of the 28 SLE patients reported by Fazzini et al…”

Section: Translational Biomedicine Issn 2172-0479mentioning

confidence: 99%

Pentraxin 3 in Systemic Lupus Erithematosus: Questions to be Resolved

Ass

Monari

Aless³

et al. 2015

Transl Biomed

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“…Originally, PTX3 was cloned as an interleukin-1-inducible gene in endothelial cells or a tumor necrosis factor-inducible gene in fibroblasts, but it can also be induced in cells of the monocyte lineage by proinflammatory cytokines (1)(2)(3). PTX3 is produced locally at sites of inflammation, and serum levels of PTX3 can be used as an independent laboratory indicator of disease activity in small-vessel vasculitis, since serum levels of PTX3 do not correlate with levels of CRP in patients with vasculitis (4).…”

Section: 7%) (P ‫؍‬ 00003) Ptx3 Was Localized Around Vessels As mentioning

confidence: 99%

Abundance of the long pentraxin PTX3 at sites of leukocytoclastic lesions in patients with small‐vessel vasculitis

Rossum

Pas

Fazzini

et al. 2006

Arthritis & Rheumatism

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Objective. The prototypical tissue pentraxin PTX3 inhibits phagocytosis of late apoptotic polymorphonuclear leukocytes (PMNs) by macrophages. Levels of PTX3 parallel disease activity in small-vessel vasculitis. Small-vessel vasculitis is often characterized by leukocytoclasia, a phenomenon of accumulation of nuclear remnants from unscavenged PMNs in or near the vessel wall. We therefore hypothesized that PTX3 accumulates at sites of leukocytoclastic vasculitis and, as such, is a key factor for the induction of leukocytoclasis.Methods. We examined skin biopsy samples from 13 patients with small-vessel vasculitis and from 4 healthy and 3 inflammatory skin disease controls. Biopsy tissues, characterized histopathologically as leukocytoclastic vasculitis, were studied for the presence of PTX3 using rabbit anti-PTX3 polyclonal antibodies. Sections were scored morphometrically for leukocytoclastic infiltrates in conjunction with PTX3 staining. Morphometric scores were expressed as percentages of staining of the total tissue area.Results. Biopsy specimens from patients with leukocytoclastic vasculitis revealed an abundant upregulation of PTX3 at sites of leukocytoclastic infiltrates. Significantly more PTX3 was found in tissues from the 13 patients with vasculitis (mean ؎ SEM 48.9 ؎ 6.1%) than in tissues from the 7 controls (4.5 ؎ 2.7%) (P ‫؍‬ 0.0003). PTX3 was localized around vessels, as well as spread diffusely throughout the tissue.Conclusion. PTX3 is abundantly present at sites of leukocytoclastic infiltrates in patients with smallvessel vasculitis, but not in controls. Since PTX3 inhibits phagocytosis of late apoptotic PMNs by macrophages and is strongly up-regulated at sites of leukocytoclastic infiltration, PTX3 is a candidate factor in the phenomenon of leukocytoclasia in small-vessel vasculitis.

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PTX3 in small-vessel vasculitides: An independent indicator of disease activity produced at sites of inflammation

Cited by 248 publications

References 37 publications

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

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

Pentraxin 3 in Systemic Lupus Erithematosus: Questions to be Resolved

Abundance of the long pentraxin PTX3 at sites of leukocytoclastic lesions in patients with small‐vessel vasculitis

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