Induction of Vascular Adhesion Protein-1 during Liver Allograft Rejection and Concomitant Cytomegalovirus Infection in Rats

Martelius, Timi; Salmi, Marko; Wu, Hsien‐Tsai; Bruggeman, Cathrien A.; Höckerstedt, Krister; Jalkanen, Sirpa; Lautenschlager, Irmeli

doi:10.1016/s0002-9440(10)64638-x

Cited by 23 publications

(18 citation statements)

References 39 publications

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“…For example, CMV infection of smooth muscle cells generates reactive oxygen species that activate NF-jB, a potent inducer of pro-inflammatory cytokines and chemokines (13). CMV-infected endothelial cells demonstrate enhanced expression of several cell surface molecules that are involved in the adhesion of leukocytes, such as ICAM-1, VCAM-1, VAP-1, E-selectin and MHC Class I antigens (9,14,15). Further more, in the presence of chemokines, such as RANTES and MCP-1, the infection induces migration of the inflammatory cells to the sites of chemokine production.…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…Of all evaluated pathogens, only IgG seropositivity to HSV-2 (p = 0.05) and IgA seropositivity to EBV (p = 0.001) as well as H. pylori (p = 0.002) revealed an independent significant association with future cardiovascular death. However, when infectious burden was evaluated, patients seropositive to > 5 pathogens compared with those seropositive to <4 pathogens had a 5.1 (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) higher risk of future cardiac death. This result was mainly driven by the pathogen burden of seropositivities to Herpes viridae (p < 0.0001).…”

Section: Total Pathogen Burdenmentioning

confidence: 99%

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The Role of Viruses in Cardiac Allograft Vasculopathy

Valantine

2004

American Journal of Transplantation

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Considerable evidence suggests a role for viruses in transplant arteriosclerosis (TA), including observational data, experimental models and therapeutic trials implicating human cytomegalovirus (HCMV) in the progression to TA. In pediatric heart transplant patients, adenoviral genome in endomyocardial biopsies (EMB) is an important predictor of TA and graft loss. During CMV viremia, EMBs from adult patients demonstrate endothelialitis and vascular smooth muscle cell proliferation. These changes are predictors of subsequent diffuse TA. HCMV immediate early proteins (IE-1 and IE-2) increase the constitutive expression of intercellular adhesion molecule-1 (ICAM-1) independent of other intracellular cytokines. Likewise, viral chemokines such as US28 have been implicated in vascular disease because of their ability to induce smooth muscle cell migration. Recent data suggests that CMV might accelerate TA through its ability to abrogate the vascular protective effects of the endothelium-derived nitric oxide system (eNOS). Confirmation of causality requires clinical trials demonstrating that antiviral agents such as ganciclovir inhibit TA. Such studies in patients though limited to retrospective analyses, suggest that ganciclovir prophylaxis early after heart transplantation reduces the risk of TA. These observations emphasize the need for randomized controlled clinical trials to confirm a causal role for CMV (and other viruses) in TA.

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Section: In Vitro Studiesmentioning

confidence: 99%

Section: Total Pathogen Burdenmentioning

confidence: 99%

The Role of Viruses in Cardiac Allograft Vasculopathy

Valantine

2004

American Journal of Transplantation

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“…[6][7][8] Animal work using neutralizing anti-VAP-1 antibodies and VAP-1-deficient mice has confirmed its importance in leukocyte trafficking during the physiologic and pathologic conditions in vivo. [9][10][11][12][13] VAP-1 belongs to a group of enzymes called semicarbazide sensitive amine oxidases (SSAOs; Enzyme Commission [EC] number 1.4.3.6). 14,15 SSAOs catalyze the general reaction R-CH 2 -NH 2 ϩ H 2 O 3 R-CH 2 -CHO ϩ H 2 O 2 ϩ NH 3 .…”

Section: Introductionmentioning

confidence: 99%

Developmental regulation of the adhesive and enzymatic activity of vascular adhesion protein-1 (VAP-1) in humans

Salmi¹,

Jalkanen

2006

Blood

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Vascular adhesion protein-1 (VAP-1) is a homodimeric glycoprotein that belongs to a unique subgroup of cell-surfaceexpressed oxidases. In adults, endothelial VAP-1 supports leukocyte rolling, firm adhesion, and transmigration in both enzyme activity-dependent and enzyme activity-independent manner. Here we studied the induction and function of VAP-1 during human ontogeny. We show that VAP-1 is already found in the smooth muscle at embryonic week 7. There are marked time-dependent switches in VAP-1 expression in the sinusoids of the liver, in the peritubular capillaries of the kidney, in the capillaries of the heart, and in the venules in the lamina propria of the gut. Fetal VAP-1 is dimerized, and it is enzymatically active. VAP-1 in fetal-type venules is able to bind cord blood lymphocytes. Also, adenovirally transfected VAP-1 on human umbilical vein endothelial cells is involved in rolling and firm adhesion of cord blood lymphocytes under conditions of physiologic shear stress. We conclude that VAP-1 is synthesized from early on in human vessels and it is functionally intact already before birth. Thus, VAP-1 may contribute critically to the oxidase activities in utero, and prove important for lymphocyte trafficking during human ontogeny. IntroductionLeukocyte trafficking between the blood and lymphoid organs is vital for the immune defense. In adults, the extravasation is governed by a multistep adhesion cascade, which involves sequential interactions between endothelial adhesion molecules and their receptors on leukocytes. 1,2 One of the endothelial molecules involved in this process is vascular adhesion protein-1 (VAP-1). It is a homodimeric 180-kDa glycoprotein expressed on vascular endothelium. [3][4][5] In vitro binding assays have shown that VAP-1 is needed for leukocyte rolling, firm adhesion, and transmigration during the extravasation cascade in adults. [6][7][8] Animal work using neutralizing anti-VAP-1 antibodies and VAP-1-deficient mice has confirmed its importance in leukocyte trafficking during the physiologic and pathologic conditions in vivo. [9][10][11][12][13] VAP-1 belongs to a group of enzymes called semicarbazide sensitive amine oxidases (SSAOs; Enzyme Commission [EC] number 1.4.3.6). 14,15 SSAOs catalyze the general reaction R-CH 2 -NH 2 ϩ H 2 O 3 R-CH 2 -CHO ϩ H 2 O 2 ϩ NH 3 . 16,17 In man and mice 3 SSAOs, VAP-1, diamine oxidase, and retina-specific amine oxidase, are known. 14,18,19 These amine oxidases are notably distinct from monoamine oxidases A and B in terms of subcellular localization, substrates, inhibitors, cofactors, and function. In fact, leukocyte-endothelial adhesion was the first physiologic function ascribed to SSAOs despite intense research of more than 50 years. Interestingly, this cellular interaction apparently takes advantage of the catalytic nature of VAP-1, since the transient but covalent bond between the enzyme (endothelial VAP-1) and substrate (a surfaceexpressed amine on leukocyte) is important for leukocyteendothelial cell interactions under conditions of sh...

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“…86,102 After liver transplantation, CMV increases inflammation in the graft and the expression of class II molecules adhesion molecules critical or T-cell activation. [103][104][105] Despite adequate treatment to resolve viremia, CMV DNA may persist in hepatocytes and bile duct epithelium. 106 As such, successful antiviral treatment of CMV infection does not exclude the persistence of the virus and the risk of chronic rejection.…”

Section: Cytomegalovirusmentioning

confidence: 99%

Infections After Orthotopic Liver Transplantation

Pedersen

Seetharam

2014

Journal of Clinical and Experimental Hepatology

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Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. ( J CLIN EXP HEPATOL 2014;4:347-360) I nfection after orthotopic liver transplantation (OLT) is a major cause of morbidity and mortality. Infection is estimated to occur in upto 80% of organ recipients. Bacterial infections are most frequent (70%), followed by viral (20%) and fungal infections (8%). 1,2,3 In addition to direct effects of infection and end-organ inflammation, pathogens may have a number of indirect effects that result in allograft injury, rejection and opportunistic superinfection.The risk of infection in liver transplant recipients is determined by the intensity of exposure to infectious agents and the overall level of immunosuppression. 4 In addition, conditions attendant to end-stage liver disease in the immediate perioperative period may render a recipient vulnerable to infection and include: neutropenia, deficits in mucocutaneous barrier integrity, presence of necrotic tissue, ischemia, diabetes mellitus, immunomodulating viruses, uremia, and protein-calorie malnutrition. 5 Infectious exposures come from many sources post liver transplant including: de novo (acquired acute) in the recipient, reactivation in the recipient, the donor organ, and nosocomial and time from transplant may provide clues to etiology (Figure 1). The overall level of immunosuppression is dependent upon the dose, duration, and choice of immunosuppression as well as underlying immune deficiencies. 6 Inflammatory responses to invading pathogens are often blunted by immunosuppressive therapy, and as a result, the classic signs or symptoms of infection may be absent. A high index of suspicion is need in the liver recipient, and a low threshold to perform invasive diagnostic procedures is often required. It is critical to identify clinical factors that predispose recipients to infection and much interest centers on identifying risk factors for infection after liver transplant. GENETIC POLYMORPHISMS IN THE INNATE IMMUNE SYSTEMIn addition to clinical factors that promote ...

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Induction of Vascular Adhesion Protein-1 during Liver Allograft Rejection and Concomitant Cytomegalovirus Infection in Rats

Cited by 23 publications

References 39 publications

The Role of Viruses in Cardiac Allograft Vasculopathy

The Role of Viruses in Cardiac Allograft Vasculopathy

Developmental regulation of the adhesive and enzymatic activity of vascular adhesion protein-1 (VAP-1) in humans

Infections After Orthotopic Liver Transplantation

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