ABSTRACT
Liver transplantation is considered to be the treatment of choice for end-stage liver disease and its success has led to an increase in the number of female liver transplant recipients who are of childbearing age. Several key issues that are noted when counselling patients who are considering pregnancy following liver transplantation include the optimal timing of pregnancy, optimal contraception methods and the management of immunosuppression during pregnancy. The present review summarizes the most recent literature so that the clinician may address these issues with their patient and enable them to make informed decisions about pregnancy planning. The authors review recent studies examining maternal and fetal outcomes, and the rates of complications including risk of graft rejection. Subsequently, the authors provide recommendations for counselling prospective mothers and the management of the pregnant liver transplant recipient.
Subject(s)
End Stage Liver Disease/therapy , Liver Transplantation , Pregnancy Complications/therapy , End Stage Liver Disease/complications , End Stage Liver Disease/immunology , Female , Humans , Immunosuppressive Agents/adverse effects , Preconception Care , Pregnancy , Pregnancy Complications/etiology , Pregnancy Outcome , Prenatal CareABSTRACT
BACKGROUND & AIMS: Infection with the rat tapeworm Hymenolepis diminuta reduces the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. Infection with H. diminuta increases colonic expression of arginase-1 and found in inflammatory zone 1 (FIZZ1), markers of alternatively activated macrophages (AAMs). We investigated whether AAMs have anticolitic effects. METHODS: Normal or macrophage-depleted Balb/c mice were infected with H. diminuta; some mice were given DNBS, and the severity of colitis was assessed by disease activity scores, myeloperoxidase activity, and histologic examination. AAMs were also differentiated in vitro, given to mice by intraperitoneal or intravenous injection, and the effects on DNBS-induced colitis were determined. Numbers of AAMs were assessed in biopsy specimens from patients with Crohn's disease. RESULTS: Depletion of intestinal macrophages using clodronate-liposomes prevented the anticolitic effect of infection with H. diminuta. Injection of AAMs, but not classically activated macrophages, significantly reduced the severity of DNBS-induced colitis. The AAM-induced, anticolitic effect was accompanied by increased interleukin (IL)-10 production from mitogen-stimulated spleen cells; in vivo neutralization of IL-10 partially reduced the effects of AAM transfer. Patients with active CD had reduced numbers of CD68(+)CD206(+) macrophages (which indicate AAM), whereas biopsy specimens from patients with inactive CD had increased numbers of these cells. CONCLUSIONS: Analysis of the H. diminuta-murine DNBS system identified the AAM, which, when administered to mice, significantly reduced DNBS-induced colitis. The ability to derive AAMs from patients' blood suggests that adoptive transfer of these cells could be a novel approach to inflammatory bowel disease.
Subject(s)
Colitis/prevention & control , Macrophage Activation , Macrophages/physiology , Animals , Arginase/genetics , Benzenesulfonates , Humans , Hymenolepiasis/immunology , Hymenolepis diminuta , Intercellular Signaling Peptides and Proteins/genetics , Interleukin-10/biosynthesis , Male , Mice , Mice, Inbred BALB C , Neutrophils/physiologyABSTRACT
Oxidized LDL (oxLDL) promotes lipid accumulation as well as growth and survival signaling in macrophages. OxLDL uptake is mainly due to scavenger receptors SR-AI/II and CD36. However, other scavenger receptors such as lectin-like oxLDL receptor-1 (LOX-1) may also play a role. We used mice with targeted inactivation of the LOX-1 gene to define the role of this receptor in the uptake of oxLDL and in activation of survival pathways. There was no difference in uptake or degradation of 125I-oxLDL in unstimulated macrophages from wild-type and LOX-1 knockout mice and no difference in the rate of clearance of oxLDL from plasma in vivo. However, when expression of LOX-1 was induced with lysophosphatidylcholine, oxLDL uptake and degradation increased 2-fold in wild-type macrophages but did not change in LOX-1 knockout macrophages. Macrophages lacking LOX-1 showed the same stimulation of PKB phosphorylation and enhancement of survival by oxLDL as wild-type cells. These data show that LOX-1 does not alter the uptake of oxLDL in unstimulated macrophages and is not essential for the pro-survival effect of oxLDL in these cells. However, LOX-1 expression is highly inducible by lysophosphatidylcholine and pro-inflammatory cytokines, and if that occurred in macrophages within atheromas, LOX-1 could substantially increase oxLDL uptake by lesion macrophages.
