Abundance of the long pentraxin PTX3 at sites of leukocytoclastic lesions in patients with small-vessel vasculitis.
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 up-regulation 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.


CONCLUSIONS
PTX3 is abundantly present at sites of leukocytoclastic infiltrates in patients with small-vessel 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.
van Rossum
Andre P
AP
University Medical Centre Groningen, Groningen, The Netherlands.
Pas
Hendri H
HH
Fazzini
Fausto
F
Huitema
Minke G
MG
Limburg
Pieter C
PC
Jonkman
Marcel F
MF
Kallenberg
Cees G M
CG
D002097:C-Reactive Protein / Q000032:analysis*; D014890:Granulomatosis with Polyangiitis / Q000378:metabolism; D006801:Humans; D011695:IgA Vasculitis / Q000378:metabolism; D008875:Middle Aged; D000683:Serum Amyloid P-Component / Q000032:analysis*; D012871:Skin Diseases / Q000378:metabolism; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000378:metabolism* / Q000473:pathology; D000099153:Pentraxins
D002097:C-Reactive Protein; D000683:Serum Amyloid P-Component; D000099153:Pentraxins