The long pentraxin PTX3 is characterized for a different gene organization and cellular source. ("Deban L - 2011") [1] PTX3 has been recently implicated in the promotion of vascular inflammation via the activation of Complement ("Castellano G - 2010") [2]
The aim of the study was to investigate the possible involvement of PTX3 in renal I/R injury.
Six rats were subjected to 45 minutes of ischemia by ligation of renal artery. Renal tissues at 2h and 5h after reperfusion were evaluated by immunofluorescence analysis.
Five pigs underwent to 30 minutes of renal warm ischemia by clamping renal artery. Multiple biopsies were performed at baseline, 15 min, 30 min, 60 min and 24 h after reperfusion. Renal sections were evaluated by confocal laser microscopy.
In the pig model, confocal laser microscopy demonstrated PTX3 deposits already at 15’of reperfusion, localized at peritubular (T15 7.7±1.1; p=0.005) and glomerular (8.2±2.5; p=0.03) capillary levels, (Figura 1) showing a specific co-localization with CD31, an endothelial cell marker. (Figura 2)
We found a significant increase in infiltrating interstitial leucocytes such as CD163+/PTX3+monocyte-macrophages (6.2±2.1; p=0.05) and SWC3a+/PTX3+dendritic cells (3.7±0.5 p=0.05) compared to T0. Finally, we identified tubulo-interstitial FSP1+/PTX3+ fibroblast(4.1±1.3; p=0.04). (Figura 3 - Figura 4)
Co-localization between C5b-9 and PTX3 on renal endothelial cells clearly demonstrated the activation of Complement system in presence of PTX3 deposits. (Figura 5)
On the contrary, the analysis of rat kidneys showed that PTX3 was not modulated by I/R injury. Rat PTX3 specifically co-localized with alpha-SMA positive cells at vascular level without any association with infiltrating leukocytes and Complement activation. (Figura 6)
This study first demonstrates a significant difference in PTX3-mediated C activation between pig and rat kidney.
The association of PTX3 with the Classical and Lectin pathways of C suggests a role for PTX3 as a potential therapeutic target to prevent C-induced renal I/R injury.
[1] Deban L, Jaillon S, Garlanda C et al. Pentraxins in innate immunity: lessons from PTX3. Cell and tissue research 2011 Jan;343(1):237-49
[2] Castellano G, Di Vittorio A, Dalfino G et al. Pentraxin 3 and complement cascade activation in the failure of arteriovenous fistula. Atherosclerosis 2010 Mar;209(1):241-7
Per inserire una domanda, segnalare la tua esperienza, un tuo commento o una richiesta di precisazione fai il login con il tuo nome utente e password.
Se non lo sei ancora puoi registrati partendo da qui.