Caveolin-1 Expression Is a Distinct Feature of Chronic Rejection-Induced Transplant Capillaropathy

Abstract

Peritubular capillary basement membrane multilayering (PTCBMML) is a pathological landmark of chronic rejection-induced transplant capillaropathy (TC), but its cellular mechanisms are not fully understood. We observed de novo caveolae formation in endothelial cells in TC under electron microscopy. To examine the role of caveolae and their structural components in TC, biopsy samples from cases of chronic rejection were double-immunostained for Caveolin-1 (Cav-1) and Pathologische Anatomie Leidenendothelium (PAL-E; a marker of peritubular capillary [PC]). Thirty-two cases of chronic rejection (group I) were compared with 18 cases of interstitial fibrosis and tubular atrophy with no evidence of any specific etiology (IF/TA; group II) and eight cases of peritubular capillaritis (group III). The Cav-1/PAL-E immunoreactivities in groups I-III (%Cav-1/PAL-E) were 41.8 ± 23.1%, 8.1 ± 7.3% (p < 0.01 vs. group I) and 12.7 ± 7.4% (p < 0.01 vs. group I), respectively. Furthermore, multiple linear regression models demonstrated that %Cav-1/PAL-E was independently associated with the PTCBMML grade and reduced PC number. No correlation was observed between %Cav-1/PAL-E and PC C4d deposition in group I. We conclude that de novo caveolae formation in PC endothelia is involved in TC in chronic rejection.

Genetic Variation in Caveolin-1 Affects Survival After Lung Transplantation

“…Yet, both the nonspecific systemic marker CRP and airway neutrophilia were decreased, and significantly less patients died because of infectious complications of all kind in the carriers of the protective GG genotype, possibly indicating a decreased overall susceptibility for infections with the GG genotype of CAV-1 (rs3807989). The increased mortality observed in this study is not unexpected as it is already demonstrated that loss of CAV-1 expression correlates with mortality in different diseases such as myocardial infarct (20), skin and breast cancer (21,22), and in renal allograft failure (23). Experimental studies also demonstrated a link with increased microbial susceptibility as CAV-1Ydeficient mice had an increased sensitivity to Pseudomonas aeruginosa infection, represented by elevated inflammatory responses and decreased neutrophil recruitment for phagocytosis, leading to an increased mortality rate (24).…”

Increased Lymphatic Vessels in Patients with Encapsulating Peritoneal Sclerosis

“…We used a reported method (18). Small pieces, 1 mm 3 in size, taken from formalin-fixed, paraffin-embedded blocks from patients with EPS were deparaffinized and rehydrated.…”

Comprehensive Investigation of the Caveolin 2 Gene: Resequencing and Association for Kidney Transplant Outcomes

“…Healthy glomerular and peritubular capillary endothelial cells have few caveolae [19], [20]. However, in chronic antibody mediated rejection, substantial numbers of caveolae are found in endothelial cells and the degree of CAV1 expression correlates with the pathological severity of rejection (graded by the Banff Score) [20], [21].…”

“…However, in chronic antibody mediated rejection, substantial numbers of caveolae are found in endothelial cells and the degree of CAV1 expression correlates with the pathological severity of rejection (graded by the Banff Score) [20], [21]. There is also abundant production of CAV1 in the glomerular endothelium of patients with glomerulonephritis [19].…”