Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo

After activation, Langerhans cells (LC), a distinct subpopulation of epidermis-resident dendritic cells, migrate from skin to lymph nodes where they regulate the magnitude and quality of immune responses initiated by epicutaneously applied antigens. Modulation of LC-keratinocyte adhesion is likely to be central to regulation of LC migration. LC express high levels of epithelial cell adhesion molecule (EpCAM; CD326), a cell-surface protein that is characteristic of some epithelia and many carcinomas and that has been implicated in intercellular adhesion and metastasis. To gain insight into EpCAM function in a physiologic context in vivo, we generated conditional knockout mice with EpCAM-deficient LC and characterized them. Epidermis from these mice contained increased numbers of LC with normal levels of MHC and costimulatory molecules and T-cell-stimulatory activity in vitro. Migration of EpCAM-deficient LC from skin explants was inhibited, but chemotaxis of dissociated LC was not. Correspondingly, the ability of contact allergen-stimulated, EpCAM-deficient LC to exit epidermis in vivo was delayed, and strikingly fewer hapten-bearing LC subsequently accumulated in lymph nodes. Attenuated migration of EpCAM-deficient LC resulted in enhanced contact hypersensitivity responses as previously described in LC-deficient mice. Intravital microscopy revealed reduced translocation and dendrite motility in EpCAM-deficient LC in vivo in contact allergen-treated mice. These results conclusively link EpCAM expression to LC motility/migration and LC migration to immune regulation. EpCAM appears to promote LC migration from epidermis by decreasing LC-keratinocyte adhesion and may modulate intercellular adhesion and cell movement within in epithelia during development and carcinogenesis in an analogous fashion

Involvement of E-Cadherin in Thymus Organogenesisand Thymocyte Maturation

AbstractWe examined the role of E-cadherin expressed by thymic epithelial cells and immature thymocytes in thymus organogenesis and thymocyte development. ECCD-1 MAb, which blocks homotypic E-cadherin interactions, inhibited epithelial organization and thymocyte development in reaggregate fetal thymic organ cultures. It also interfered with the differentiation of fetal liver cells or fetal thymocytes within deoxyguanosine-treated thymic lobes, but did not affect thymocyte development in intact cultured fetal thymic lobes. In contrast, antibodies that selectively inhibit interactions between E-cadherin and αEβ7 integrins did not perturb thymic epithelial organization or thymocyte development, suggesting that homotypic E-cadherin interactions play an important role in thymus development and function

A causal model of radiating stellar collapse

We find a simple exact model of radiating stellar collapse, with a shear-free and non-accelerating interior matched to a Vaidya exterior. The heat flux is subject to causal thermodynamics, leading to self-consistent determination of the temperature $T$. We solve for $T$ exactly when the mean collision time $\tau_{c}$ is constant, and perturbatively in a more realistic case of variable $\tau_{c}$. Causal thermodynamics predicts temperature behaviour that can differ significantly from the predictions of non-causal theory. In particular, the causal theory gives a higher central temperature and greater temperature gradient.Comment: Latex [ioplppt style] 9 pages; to appear Class. Quantum Gra

D-Dimensional Radiative Plasma: A Kinetic Approach

The covariant kinetic approach for the radiative plasma, a mixture of a relativistic moving gas plus radiation quanta (photons, neutrinos, or gravitons) is generalized to D spatial dimensions. The operational and physical meaning of Eckart's temperature is reexamined and the D-dimensional expressions for the transport coefficients (heat conduction, bulk and shear viscosity) are explicitly evaluated to first order in the mean free time of the radiation quanta. Weinberg's conclusion that the mixture behaves like a relativistic imperfect simple fluid (in Eckart's formulation) depends neither on the number of spatial dimensions nor on the details of the collisional term. The case of Thomson scaterring is studied in detail, and some consequences for higher dimensional cosmologies are also discussed.Comment: 28 pages, 1 figure, uses REVTE

Exact non-equilibrium solutions of the Einstein-Boltzmann equations. II

We find exact solutions of the Einstein-Boltzmann equations with relaxational collision term in FRW and Bianchi I spacetimes. The kinematic and thermodynamic properties of the solutions are investigated. We give an exact expression for the bulk viscous pressure of an FRW distribution that relaxes towards collision-dominated equilibrium. If the relaxation is toward collision-free equilibrium, the bulk viscosity vanishes - but there is still entropy production. The Bianchi I solutions have zero heat flux and bulk viscosity, but nonzero shear viscosity. The solutions are used to construct a realisation of the Weyl Curvature Hypothesis.Comment: 16 pages LaTex, CQG documentstyle (ioplppt

Interleukin 1α Promotes Th1 Differentiation and Inhibits Disease Progression in Leishmania major–susceptible BALB/c Mice

Protective immunity against pathogens such as Leishmania major is mediated by interleukin (IL)-12–dependent Th1-immunity. We have shown previously that skin-dendritic cells (DCs) from both resistant C57BL/6 and susceptible BALB/c mice release IL-12 when infected with L. major, and infected BALB/c DCs effectively vaccinate against leishmaniasis. To determine if cytokines other than IL-12 might influence disease outcome, we surveyed DCs from both strains for production of a variety of cytokines. Skin-DCs produced significantly less IL-1α in response to lipopolysaccharide/interferon γ or L. major when expanded from BALB/c as compared with C57BL/6 mice. In addition, IL-1α mRNA accumulation in lymph nodes of L. major–infected BALB/c mice was ∼3-fold lower than that in C57BL/6 mice. Local injections of IL-1α during the first 3 d after infection led to dramatic, persistent reductions in lesion sizes. In L. major–infected BALB/c mice, IL-1α administration resulted in increased Th1- and strikingly decreased Th2-cytokine production. IL-1α and IL-12 treatments were similarly effective, and IL-1α efficacy was strictly IL-12 dependent. These data indicate that transient local administration of IL-1α acts in conjunction with IL-12 to influence Th-development in cutaneous leishmaniasis and prevents disease progression in susceptible BALB/c mice, perhaps by enhancing DC-induced Th1-education. Differential production of IL-1 by C57BL/6 and BALB/c mice may provide a partial explanation for the disparate outcomes of infection in these mouse strains

Exact inhomogeneous cosmologies whose source is a radiation-matter mixture with consistent thermodynamics

We derive a new class of exact solutions of Einstein's equations providing a physically plausible hydrodynamical description of cosmological matter in the radiative era ($10^6 K > T > 10^3 K$), between nucleosynthesis and decoupling. The solutions are characterized by the Lema\^{\i}tre-Tolman -Bondi metric with a viscous fluid source, subjected to the following conditions: (a) the equilibrium state variables satisfy the equation of state of a mixture of an ultra-relativistic and a non-relativistic ideal gases, where the internal energy of the latter has been neglected, (b) the particle numbers of the mixture components are independently conserved, (c) the viscous stress is consistent with the transport equation and entropy balance law of Extended Irreversible Thermodynamics, with the coefficient of shear viscosity provided by Kinetic Theory for the `radiative gas' model. The fulfilment of (a), (b) and (c) restricts initial conditions in terms of an initial value function, $\Delta_i^{(s)}$, related to the average of spatial gradients of the fluctuations of photon entropy per baryon in the initial hypersurface. Constraints on the observed anisotropy of the microwave cosmic radiation and the condition that decoupling occurs at $T=T_{_D}\approx 4\times 10^3$ K yield an estimated value: $|\Delta_i^{(s)}|\approx 10^{-8}$ which can be associated with a bound on promordial entropy fluctuations. The Jeans mass at decoupling is of the same order of magnitude as that of baryon dominated perturbation models ($\approx 10^{16} M_\odot$)Comment: LaTeX with revtex (PRD macros). Contains 9 figures (ps). To be published in Physics Review

Cosmological particle production, causal thermodynamics, and inflationary expansion

Combining the equivalence between cosmological particle creation and an effective viscous fluid pressure with the fact that the latter represents a dynamical degree of freedom within the second-order Israel-Stewart theory for imperfect fluids, we reconsider the possibility of accelerated expansion in fluid cosmology. We find an inherent self-limitation for the magnitude of an effective bulk pressure which is due to adiabatic (isentropic) particle production. For a production rate which depends quadratically on the Hubble rate we confirm the existence of solutions which describe a smooth transition from inflationary to noninflationary behavior and discuss their interpretation within the model of a decaying vacuum energy density. An alternative formulation of the effective imperfect fluid dynamics in terms of a minimally coupled scalar field is given. The corresponding potential is discussed and an entropy equivalent for the scalar field is found.Comment: 16 pages, revtex file, submitted to Phys. Rev.

Reheating and causal thermodynamics

The reheating process in inflationary universe models is considered as an out-of-equilibrium mixture of two interacting and reacting fluids, and studied within the framework of causal, irreversible thermodynamics. The evolution of the temperature and the decay rate as determined by causal thermodynamics are estimated at different stages of the process. A simple model is also used to find the perturbations of the expansion rate, including the possibility of damped oscillations.Comment: 11 pages, Revtex, submitted to Phys.Rev.

Abnormal Placental Development and Early Embryonic Lethality in EpCAM-Null Mice

BACKGROUND: EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs