Number Of Cell Adhesion Molecules Research Articles

Extracellular Matrix Expression in Human Induced Pluripotent Stem Cell-Derived Optic Vesicles

Background: Human tissue/organ development is a complex, highly orchestrated process, regulated in part by the surrounding extracellular matrix (ECM). Every complex tissue, including the retina, has a unique ECM configuration that plays a critical role in cellular differentiation, adhesion, migration, and maturation. Aim: To characterize ECM expression of human induced pluripotent stem cell-derived optic vesicles (iPSC-OVs). Methods: A 3- dimensional (3D) in vitro suspension culture system was used to direct differentiation of human induced pluripotent stem cells (iPSCs) into optic vesicles (OVs). Stepwise differentiation of iPSCs into retinal progenitor cells was confirmed by sequential expression of OTX2, SOX1, SIX6, LHX2, PAX6, and CHX10. Expression of ECM genes in iPSC-derived OVs was analyzed by RT2 ProfilerTM PCR Array, whereas immunofluorescence staining was performed to detect ECM proteins in the OVs. Results: A number of cell adhesion molecules (CAMs) previously reported to be abundantly expressed in iPSCs such as E-cadherin, Intercellular adhesion molecule-1 (ICAM1), Integrin-α L, Integrin-α M, Integrin-α 6 were downregulated while neural and retina specific CAMs including neural cell adhesion molecule 1 (NCAM1), neural plakophilin-related armadillo repeat protein (NPRAP), Integrin-α 1 and Integrin-α 4 were upregulated. Several glycoproteins that have been reported to play key roles during retinogenesis, namely CD44, Tenascin C, Tenascin R, Neurocan, Neuroglycan C, Delta 2 Catenin, Vitronectin, and Reelin were also present. Conclusion: We have identified an array of ECM proteins that were expressed during retinogenesis. Further characterization of these proteins will lead to a better understanding of retinal development.

Proteomic profile of human stem cells from dental pulp and periodontal ligament

BackgroundThe study of molecular profiling of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) contributes to understanding the high proliferation ability and multi-lineage differentiation potential.ObjectivesThe aim of the study was to compare the protein abundance and specific markers of DPSCs and PDLSCs by protein profiles.Material and methodsThe DPSCs and PDLSCs extracted from the same tooth were lysed with 3 biological replicates and the protein was collected. Two-dimensional electrophoresis technology and TMT proteomics were used to separate and identify proteins. The data are available via ProteomeXchange with identifier PXD021997. The RT-qPCR detection of mRNA expression revealed a special marker for distinguishing two kinds of dental stem cells.ResultsCompared with PDLSCs, 962 differential proteins (DAPs) were up-regulated, and 127 were down-regulated in DPSCs. In the up-regulated DAPs, two high-scoring sub-networks were detected for neural-related molecules, which encode cell vesicle transport and mitochondrial energy transfer to regulate cell proliferation and secretion factors. A large number of cell adhesion molecules were distinguished among the highly expressed molecules of PDLSCs, supporting that stem cells provide cell attachment functions. It was interpreted ENPL, HS90A and HS90B were highly expressed in DPSCs, while CKB was highly abundant in PDLSCs. Another cell group confirmed that these molecules can be used as special biomarkers to identify and distinguish between DPSCs and PDLSCs.ConclusionsThis study can promote the basic research and clinical application of dental stem cells.SignificanceThe high-throughput protein profiles were tested by combining two-dimensional gel proteomics and TMT-based proteomics. The proteomics of DPSCs and PDLSCs without individual difference demonstrated an accurate and comprehensive molecular expression profiles and interpretation of neural application potential, this study promotes the basic research of dental stem cells and clinical application.

The Emerging Role of Mechanics in Synapse Formation and Plasticity.

The regulation of synaptic strength forms the basis of learning and memory, and is a key factor in understanding neuropathological processes that lead to cognitive decline and dementia. While the mechanical aspects of neuronal development, particularly during axon growth and guidance, have been extensively studied, relatively little is known about the mechanical aspects of synapse formation and plasticity. It is established that a filamentous actin network with complex spatiotemporal behavior controls the dendritic spine shape and size, which is thought to be crucial for activity-dependent synapse plasticity. Accordingly, a number of actin binding proteins have been identified as regulators of synapse plasticity. On the other hand, a number of cell adhesion molecules (CAMs) are found in synapses, some of which form transsynaptic bonds to align the presynaptic active zone (PAZ) with the postsynaptic density (PSD). Considering that these CAMs are key components of cellular mechanotransduction, two critical questions emerge: (i) are synapses mechanically regulated? and (ii) does disrupting the transsynaptic force balance lead to (or exacerbate) synaptic failure? In this mini review article, I will highlight the mechanical aspects of synaptic structures—focusing mainly on cytoskeletal dynamics and CAMs—and discuss potential mechanoregulation of synapses and its relevance to neurodegenerative diseases.

Diagnostic and prognostic value of assessment of soluble adhesion molecules sICAM-1 and sVCAM-1 in septic patients

The review is devoted to the assessment of use of cell adhesion molecules including intercellular adhesion molecule type 1 (ICAM-1) and vascular cell adhesion molecule type 1 (VCAM-1) as additional laboratory markers for severity assessment and as predictors of outcome in septic patients. One of the very important pathogenetic components of this state is known to be endothelium activation replaced by its dysfunction. The level of expression of these molecules on endothelial cell membrane affects leukocyte migration from the vessels to surrounding tissues. Besides, a number of cell adhesion molecules are expressed on immunocompetent cells that influences the development of immune response (both innate and acquired). The main characteristics of ICAM-1 and VCAM-1 are presented, including the possibility of soluble forms formation (sICAM-1, sVCAM-1) due to shedding of cell membrane induced by proteolytic enzymes. The results of literature analysis demonstrate that in sepsis the serum content of sICAM-1 and sVCAM-1 is significantly higher than in healthy subjects. In most cases their level is higher than in patients with other critical states (such as severe infectious inflammatory processes, myocardial infarction, stroke, burns, etc.) that according to some authors allows their using for differential diagnosis of sepsis and other critical states. There is no consensus on correlation with disease severity (sepsis, severe sepsis, septic shock), presence of multiple organ failure and its prediction, and lethal outcomes. Results inconsistency most probably can be explained by differences in study design. Nevertheless, continuing studies in this direction is considered perspective.

Effects of selection for ethanol preference on gene expression in the nucleus accumbens of HS-CC mice.

Previous studies on changes in murine brain gene expression associated with the selection for ethanol preference have used F2 intercross or heterogeneous stock (HS) founders, derived from standard laboratory strains. However, these populations represent only a small proportion of the genetic variance available in Mus musculus. To investigate a wider range of genetic diversity, we selected mice for ethanol preference using an HS derived from the eight strains of the collaborative cross. These HS mice were selectively bred (four generations) for high and low ethanol preference. The nucleus accumbens shell of naive S4 mice was interrogated using RNA sequencing (RNA-Seq). Gene networks were constructed using the weighted gene coexpression network analysis assessing both coexpression and cosplicing. Selection targeted one of the network coexpression modules (greenyellow) that was significantly enriched in genes associated with receptor signaling activity including Chrna7, Grin2a, Htr2a and Oprd1. Connectivity in the module as measured by changes in the hub nodes was significantly reduced in the low preference line. Of particular interest was the observation that selection had marked effects on a large number of cell adhesion molecules, including cadherins and protocadherins. In addition, the coexpression data showed that selection had marked effects on long non-coding RNA hub nodes. Analysis of the cosplicing network data showed a significant effect of selection on a large cluster of Ras GTPase-binding genes including Cdkl5, Cyfip1, Ndrg1, Sod1 and Stxbp5. These data in part support the earlier observation that preference is linked to Ras/Mapk pathways.

Local translation of cell adhesion molecules in axons.

During development and regeneration, axonal growth depends on a rapid response to extracellular growth and guidance molecules. One mechanism underlying this rapid response is local protein synthesis (Jung et al., 2012). Local protein synthesis is a highly tuned, multi-step process by which mRNA binding proteins bind to specific sequences within the untranslated regions of particular mRNAs in the soma; mRNAs are then transported to axons and growth cones and translated at the appropriate spatial location in response to specific guidance cues. Many studies have now demonstrated that stimulus-induced local translation is critical to appropriate axon growth, guidance and regeneration. Multiple types of proteins are locally translated within axons, including those regulating the cytoskeleton, retrograde signaling, regeneration and cellular survival.

Neural cell adhesion molecule differentially interacts with isoforms of the fibroblast growth factor receptor

The fibroblast growth factor receptor (FGFR) can be activated through direct interactions with various fibroblast growth factors or through a number of cell adhesion molecules, including the neural cell adhesion molecule (NCAM). We produced recombinant proteins comprising the ligand-binding immunoglobulin-like modules 2 and 3 of FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR3c, and FGFR4, and found that all FGFR isoforms, except for FGFR4, interacted with NCAM. The binding affinity of NCAM-FGFR interactions was considerably higher for splice variant 'b' than for splice variant 'c'. We suggest that the expression pattern of various FGFR isoforms determines the cell context-specific effects of NCAM signaling through FGFR.

Immobilized Pool of NCAM180 in the Postsynaptic Membrane Is Homeostatically Replenished by the Flux of NCAM180 from Extrasynaptic Regions

Homeostatic mechanisms maintaining high levels of adhesion molecules in synapses over prolonged periods of time remain incompletely understood. We used fluorescence recovery after photobleaching experiments to analyze the steady state turnover of the immobile pool of green fluorescent protein-labeled NCAM180, the largest postsynaptically accumulating isoform of the neural cell adhesion molecule (NCAM). We show that there is a continuous flux of NCAM180 to the postsynaptic membrane from nonsynaptic regions of dendrites by diffusion. In the postsynaptic membrane, the newly delivered NCAM180 slowly intermixes with the immobilized pool of NCAM180. Preferential immobilization and accumulation of NCAM180 in the postsynaptic membrane is reduced after disruption of the association of NCAM180 with the spectrin cytoskeleton and in the absence of the homophilic interactions of NCAM180 in synapses. Our observations indicate that the homophilic interactions and binding to the cytoskeleton promote immobilization of NCAM180 and its accumulation in the postsynaptic membrane. Flux of NCAM180 from extrasynaptic regions and its slow intermixture with the immobile pool of NCAM180 in the postsynaptic membrane may be important for the continuous homeostatic replenishment of NCAM180 protein at synaptic contacts without compromising the long term synaptic contact stability.

Neuritogenic and Neuroprotective Properties of Peptide Agonists of the Fibroblast Growth Factor Receptor

Fibroblast growth factor receptors (FGFRs) interact with their cognate ligands, FGFs, and with a number of cell adhesion molecules (CAMs), such as the neural cell adhesion molecule (NCAM), mediating a wide range of events during the development and maintenance of the nervous system. Determination of protein structure, in silico modeling and biological studies have recently resulted in the identification of FGFR binding peptides derived from various FGFs and NCAM mimicking the effects of these molecules with regard to their neuritogenic and neuroprotective properties. This review focuses on recently developed functional peptide agonists of FGFR with possible therapeutic potential.

Synapse formation and remodeling

Synapses are specialized structures that mediate information flow between neurons and target cells, and thus are the basis for neuronal system to execute various functions, including learning and memory. There are around 10(11) neurons in the human brain, with each neuron receiving thousands of synaptic inputs, either excitatory or inhibitory. A synapse is an asymmetric structure that is composed of pre-synaptic axon terminals, synaptic cleft, and postsynaptic compartments. Synapse formation involves a number of cell adhesion molecules, extracellular factors, and intracellular signaling or structural proteins. After the establishment of synaptic connections, synapses undergo structural or functional changes, known as synaptic plasticity which is believed to be regulated by neuronal activity and a variety of secreted factors. This review summarizes recent progress in the field of synapse development, with particular emphasis on the work carried out in China during the past 10 years (1999-2009).

Intraretinal projection of retinal ganglion cell axons as a model system for studying axon navigation

The initial step of retinal ganglion cell (RGC) axon pathfinding involves directed growth of RGC axons toward the center of the retina, the optic disc, a process termed “intraretinal guidance”. Due to the accessibility of the system, and with various embryological, molecular and genetic approaches, significant progress has been made in recent years toward understanding the mechanisms involved in the precise guidance of the RGC axons. As axons are extending from RGCs located throughout the retina, a multitude of factors expressed along with the differentiation wave are important for the guidance of the RGC axons. To ensure that the RGC axons are oriented correctly, restricted to the optic fiber layer (OFL) of the retina, and exit the eye properly, different sets of positive and negative factors cooperate in the process. Fasciculation mediated by a number of cell adhesion molecules (CAMs) and modulation of axonal response to guidance factors provide additional mechanisms to ensure proper guidance of the RGC axons. The intraretinal axon guidance thus serves as an excellent model system for studying how different signals are regulated, modulated and integrated for guiding a large number of axons in three-dimensional space.

Slug Regulates Integrin Expression and Cell Proliferation in Human Epidermal Keratinocytes

The human epidermis is a self-renewing epithelial tissue composed of several layers of keratinocytes. Within the epidermis there exists a complex array of cell adhesion structures, and many of the cellular events within the epidermis (differentiation, proliferation, and migration) require that these adhesion structures be remodeled. The link between cell adhesion, proliferation, and differentiation within the epidermis is well established, and in particular, there is strong evidence to link the process of terminal differentiation to integrin adhesion molecule expression and function. In this paper, we have analyzed the role of a transcriptional repressor called Slug in the regulation of adhesion molecule expression and function in epidermal keratinocytes. We report that activation of Slug, which is expressed predominantly in the basal layer of the epidermis, results in down-regulation of a number of cell adhesion molecules, including E-cadherin, and several integrins, including alpha3, beta1, and beta4. We demonstrate that Slug binds to the alpha3 promoter and that repression of alpha3 transcription by Slug is dependent on an E-box sequence within the promoter. This reduction in integrin expression is reflected in decreased cell adhesion to fibronectin and laminin-5. Despite the reduction in integrin expression and function, we do not observe any increase in differentiation. We do, however, find that activation of Slug results in a significant reduction in keratinocyte proliferation.

Presenilin-dependent Processing and Nuclear Function of γ-Protocadherins

The recently described protocadherin gene clusters encode cadherin-related proteins, which are highly expressed in the vertebrate nervous system. Here, we report biochemical studies addressing proteolytic processing of gamma-protocadherins. These type-I transmembrane proteins are cleaved by a metalloproteinase in vivo, generating a soluble extracellular fragment and a carboxyl-terminal fragment associated with the cellular membrane. In addition, we show that the carboxyl-terminal fragment is a substrate for further cleavage mediated by presenilin. Consequently, accumulation of the fragment is found when gamma-secretase is inactivated either by the specific presenilin-inhibitor L685,458 or in double mutant murine embryonic fibroblasts lacking both presenilin genes. The gamma-secretase-generated carboxyl-terminal fragment is largely unstable but accumulates when proteasomal degradation is inhibited. Interestingly, the proteolytic fragment generated by gamma-secretase can localize to the nucleus. This is the first report providing experimental evidence for a cell surface receptor signaling function of protocadherins regulated by proteolytic events.

Neural cell adhesion molecules - brain glue and much more

The formation of stable cell contacts is of pivotal importance for every metazoan life form. It is therefore not surprising that adhesive molecules appeared early during the evolution of multicellular organisms. The pioneering work of Johannes Holtfreter and others indicated that adhesive molecules, which reside in the plasma membrane on the surface of most cells, are not only important for establishing general cell adhesion and cellular contacts, but also convey a specific tissue and cellular identity to their host cells (1). Over the last few decades a large number of cell adhesion molecules (CAMs) have been identified and further characterized, and we have learned that the expression of these proteins is highly choreographed in terms of timing and cell identity.

Targeting drug delivery to radiation-induced neoantigens in tumor microvasculature

Radiation can be used to guide drugs to specific sites such as neoplasms or aberrant blood vessels. When blood vessels are treated with ionizing radiation, they respond by expressing a number of cell adhesion molecules and receptors that participate in homeostasis. Examples of radiation-induced molecules in blood vessels include ICAM-1, E-selectin, P-selectin and the β 3 integrin. We have observed that the endothelium and blood components respond to oxidative stress in a similar, if not identical manner in all tumor models. Although we have identified several other radiation-induced molecules within tumor blood vessels, the β 3 target for drug delivery achieves the greatest site-specific peptide binding within irradiated tumor blood vessels. We have focused on peptides and antibodies that bind to integrin β 3. β 3-binding proteins have been conjugated to fluorochromes and radionuclides to study the site specificity and microscopic distribution. We have found immunofluorescent and immunohistochemical staining of β 3 within the lumen of blood vessels immediately following irradiation. To determine whether it is feasible to guide drug delivery to irradiated tumors, we studied ligands to α 2bβ 3 (fibrinogen). Peptides within fibrinogen that bind to α 2bβ 3 includes the dodecapeptide, HHLGGAKQAGDV and the RGD peptide. We utilized 131I conjugation to these ligands to study the biodistribution in tumor bearing mice. Our clinical trial consists of the RGD peptidomimetic, biapcitide, labeled with 99mTc. This study shows that it is feasible to guide drugs to human neoplasms by use of radiation-guided peptides. These studies have shown that peptides that bind to these integrins bind to tumors following exposure to ionizing radiation.

The contribution of adhesion molecule expression in donor kidney biopsies to early allograft dysfunction.

Renal allograft rejection is associated with the expression of adhesion molecules on vascular endothelial and tubular epithelial cells. To assess whether the number of cell adhesion molecules expressed in donor kidneys can predict early rejection or delayed graft function, kidney biopsies from 20 living and 53 cadaveric kidney donors were obtained before engraftment into the recipients and the expression of the cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were determined by immunohistochemistry. All biopsies from living donors showed significantly lower expression of ICAM-1 and VCAM-1 compared to biopsies from cadaveric donors. There was no difference in the expression of adhesion molecules on tubular cells between transplants with primary function compared to allografts with early rejection in living donated kidneys (ICAM-1: 2+/-8 vs. 3+/-8%; VCAM-1: 9+/-7 vs. 1+/-1%), as well as in cadaveric kidneys (ICAM-1: 38+/-29 vs. 39+/-38%; VCAM-1: 55+/-27 vs. 48+/-29%). The expression of ICAM-1 molecules on tubular cells was determined to be a predictor for the occurrence of delayed graft function in cadaveric kidneys (ICAM-1: 65+/-24* vs. 38+/-29% delayed graft versus primary graft function). No delayed graft function occurred in recipients of living donated kidneys. These data suggest that adhesion molecule expression in donor biopsies is not a predictor for early allograft rejection, but can be used as a marker for the development of postischemic acute renal allograft failure.

Intestinal Cell Adhesion Molecules: Liver‐Intestine Cadherin

The cadherin superfamily comprises a large number of cell adhesion molecules, several of which are expressed in the gastrointestinal tract. LI-cadherin represents a novel type of cadherin within the cadherin superfamily distinguished from other cadherins by structural and functional features described in this review. In the mouse and human, LI-cadherin is selectively expressed on the basolateral surface of enterocytes and goblet cells in the small and large intestine, whereas in the rat this cadherin is additionally detectable in hepatocytes. LI-cadherin is capable of mediating Ca(2+)-dependent homophilic cell-cell adhesion independent of interactions with the cytoskeleton, indicating that the adhesive function of this novel cadherin is complementary to that of E-cadherin and desmosomal cadherins co expressed in the intestinal mucosa.

Ninjurin2, a Novel Homophilic Adhesion Molecule, Is Expressed in Mature Sensory and Enteric Neurons and Promotes Neurite Outgrowth

A large number of cell adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interaction during development, differentiation and regeneration of the peripheral nervous system. Here, we report the identification of a novel cell surface adhesion molecule, ninjurin2 (for nerve injury induced protein 2). Ninjurin2 is a homolog of a homophilic cellular adhesion molecule, ninjurin1, that was previously isolated as a gene induced in Schwann cells after nerve injury. Ninjurin1 and 2 share conserved hydrophobic regions for their transmembrane domains; however, they do not contain comparable adhesion motifs nor do they interact with each other. In the peripheral nervous system, ninjurin2 is expressed constitutively in mature sensory and enteric neurons but not in glial cells or in autonomic ganglia. Ninjurin2 is upregulated in Schwann cells surrounding the distal segment of injured nerve with a time course similar to that of ninjurin1, neural CAM, and L1. Ninjurin2 promotes neurite outgrowth from primary cultured dorsal root ganglion neurons, presumably via homophilic cellular interactions. Ninjurin2 is also highly expressed in hematopoietic and lymphatic tissues. Finally, the ninjurin2 gene is located on human chromosome 12p13 in which several disorders of unknown etiology have been mapped, including inflammatory bowel disease and acrocallosal syndrome.

The role of glycosphingolipids in neurological disorders. Mechanisms of immune action.

Specific criteria that are required for understanding the significance of glycosphingolipid (GSL) antibodies, as well as mechanisms that may underlie the immunopathogenesis of these disorders, are proposed. These criteria are illustrated by describing the role of a unique family of acidic GSLs, the sulfated glucuronosyl glycolipids (SGGLs), in the pathogenic mechanisms of peripheral neuropathy with IgM paraproteinemia. High anti-SGGL antibody titers are detected in patients suffering from this disorder. It is demonstrated that SGGLs, which possess a common carbohydrate epitope with myelin-associated glycoprotein (MAG), several low-molecular-weight glycoproteins in the PNS, and a number of cell adhesion molecules, are potential target antigens for the neuropathy. Evidence is provided that sensitization of laboratory animals with pure SGGLs elicits experimental peripheral neuropathies that exhibit remarkable similarities with respect to antibody specificity, and electrophysiological and pathological features to the human conditions. By intraneural injection of antibodies into the sciatic nerve of rats, it is demonstrated that pathological changes consisting of demyelination and axonal degeneration are mediated by an antibody- and complement-dependent process. To elucidate the mechanisms of antibody penetration from circulation into the endoneurial space, it is further shown that brain microvascular endothelial cells express SGGLs. Moreover it has been found that inflammatory cytokines are capable of upregulating the expression of SGGLs on the endothelial cell surface, resulting in a greater attachment of leukocytes. This latter observation suggests that SGGLs may also participate in cell-mediated responses in certain inflammatory neurological disorders.

Suppression of PBC-like hepatic lesions in murine GVHR model by antibodies against adhesion molecules

Background: We have previously demonstrated that Thl type cytokine mRNA firstly increased and Th2 type cytokine mRNA elevated subsequently in liver infiltrating CD4 ÷ T cells of PBC-like hepatic lesion using murine GVHR (Gastroenterology, 110, A1219, 1996). A number of cell adhesion molecules are important for CD4 ÷ T ceils to infiltrate the liver. Moreover, we have also shown that antibodies against adhesion molecules such as LFA-1 and VLA-4 suppressed the formation of PBC-like lesions (Hepatology, 22 (4) pt.2, 1995, Gastroenterology 110 (4) A1235, 1996). However, the precise molecular mechanism of these suppressions by the administration of antibodies against adhesion molecules still remains unknown. Aim: To clarify whether Thl/Th2 balance is related to the suppression of PBC-like hepatic lesions by antibodies against adhesion molecules. Methods: Sex-matched 1 x 107 C57BL/6 (B6) T spleen cells were injected into (B6.C-H-2 bml2 x B6) F 1 mice intravenously. Each 50 lag of anti-mouse t~ chain of VLA-4 mAb (PS2.3), anti-mouse VCAM-1 mAb (MK/2) or normal rat IgG were administered intraperitoneally per mouse during cell transfer. All mice were sacrificed 2 weeks after the first cell transfer. 1 x 10 -s liver infiltrating Thy 1.2+CD4 ÷ lymphocytes were sorted using FACS vantage and the RNA was isolated by AGPC method. A semiquantitative RT-PCR was carried out using primers specific for IL-2, IFN~, IL-4, IL-10. Immunohistochemical, HE staining, and ELISA for AMA were examined. Results: 1) H.E. staining showed the grade of portal cellular infiltration in the group administered both anti-VLA-4 mAbs and anti-VCAM-1 mAbs was significantly suppressed compared with the control administered normal rat IgG. The grade in the group administered just anti-VLA-4 mAbs was also suppressed compared with the control. 2) The induction of GVHR and the elevation of AMA titer were not affected in these groups by administering mAbs. 3) The expressions of IL-2, IFN'/, IL-4 and IL-10 mRNA were not changed in these groups. 4) Immunohistochemically, CD4, CDS, B220 or Mac-1 positive cells were detected in these groups. Conclusion: Although the administration against adhesion molecules did not suppress the induction of GVHR and the elevation of AMA titer, the portal cellular infiltration is reduced by just the administration of antibodies against VLA-4 in this model. However, cytokine profile of liver infiltrating CD4 ÷ T ceils and the presence of infiltrating ceils such as CD4, CD8, B220 or Mac-1 positive cells were not changed. In conclusion, it is suggested that the administration of antibodies against adhesion molecule could suppress PBC-like lesions without affecting Th 1/Th2 balance.