Biomedical subjects

S M Albelda

Publications and source records attributed to S M Albelda.

At least 109 records · Page 6Linked to original sources

PubMed1993

Basic fibroblast growth factor modulates integrin expression in microvascular endothelial cells.

During angiogenesis capillary endothelial cells undergo a coordinated set of modifications in their interactions with extracellular matrix components. In this study we have investigated the effect of the prototypical angiogenic factor basic fibroblast growth factor (bFGF) on the expression and function of several integrins in microvascular endothelial cells. Immunoprecipitation experiments with antibodies to individual subunits indicated that microvascular cells express at their surface several integrins. These include the alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 laminin/collagen receptors; the alpha 6 beta 1 laminin receptor; the alpha 5 beta 1 and alpha v beta 1 fibronectin receptors; the alpha 6 beta 4 basement membrane receptor; and the alpha v beta 3 and alpha v beta 5 vitronectin receptors. Treatment with bFGF caused a significant increase in the surface expression of the alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1, alpha 6 beta 4, and alpha v beta 5 integrins. In contrast, the level of expression of the alpha 1 beta 1 and alpha v beta 3 integrins was decreased in bFGF-treated cells. Immunoprecipitation of metabolically labeled cells indicated that bFGF increases the biosynthesis of the alpha 3, alpha 5, alpha 6, beta 4, and beta 5 subunits and decreases the production of the alpha v and beta 3 subunits. These results suggest that bFGF modulates integrin expression by altering the biosynthesis of individual alpha or beta subunits. In accordance with the upregulation of several integrins observed in bFGF-treated cells, these cells adhered better to fibronectin, laminin, vitronectin, and type I collagen than did untreated cells. The largest differences in beta 1 integrin expression occurred approximately 72 h after exposure to bFGF, at a time when the expression of the endothelial cell-to-cell adhesion molecule endoCAM was also significantly upregulated. In contrast, a shorter exposure to bFGF (24-48 h) was required for the maximal induction of plasminogen activator production in the same cells. Taken together, these results show that bFGF causes significant changes in the level of expression and function of several integrins in microvascular endothelial cells.

Adrenal Cortex↗

PubMed1993

Expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during melanoma-induced angiogenesis in vivo.

Recent ultrastructural data indicate that tumor-induced angiogenesis involves polarized outgrowth of endothelial cells from established vessels into tumor parenchyma and interstitium. Efforts to define the cytoarchitecture of the angiogenic response and to ascertain molecular determinants of polarized endothelial migration have been impeded by lack of sensitive and specific immunologic markers for endothelium and vessel wall components. In this study, we utilized monoclonal antibody to platelet-endothelial cell adhesion molecule-1 (PECAM-1), a cell-cell adhesion molecule belonging to the immunoglobulin superfamily, to determine extent and patterns of angiogenesis in metastatic melanomas before (N = 7) and after (N = 3) induction of tumor-infiltrating lymphocyte responses provoked by administration of experimental melanoma vaccine. PECAM-1 proved to be a more reliable marker for angiogenesis than antibodies to von Willebrand Factor. Although both normal and tumor vessels exhibited prominent staining for PECAM-1, different patterns of endothelial reactivity were observed. Formation of new vessels was associated with i) PECAM-1 redistribution from a constitutive circumferential membrane pattern to a pattern restricted to cell-cell junctions; ii) formation of endothelial cords formed by cell-cell interactions; and iii) eventual development of open lumens. Vessels within inflamed (vaccine-treated) and non-inflamed melanomas did not differ with regard to patterns of PECAM-1 expression. Forming vessels of inflamed melanomas failed to express the cytokine-inducible activation marker, E-selectin. Although normal microvessels and reactive vessels of healing wounds demonstrated prominent staining for alpha 6 laminin receptor, vessels within melanomas showed apparently diminished expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Adhesion molecules in the lung. An overview.

Several distinct cell adhesion molecule families have recently been identified and found to be important in the inflammatory response and for epithelial and endothelial homeostasis. The integrin family of adhesion molecules functions in both cell-matrix and cell-cell interactions, whereas the cadherins serve as important cell-cell receptors for maintenance of epithelial integrity. The leukocyte integrins, selectins, members of the immunoglobulin supergene family, and specific carbohydrates mediate adhesive interactions between leukocytes and endothelial cells. The mechanisms of leukocyte-epithelial adhesion are less well understood, but integrins and members of the immunoglobulin supergene family are also involved. The role of these molecules in pulmonary structure and inflammation is currently being actively explored. Further knowledge of these interactions, and the interplay of adhesion molecules, cytokines, and chemoattractants is likely to lead to novel therapeutic modalities in inflammatory diseases of the airway and lung parenchyma. In this overview, the families of adhesion molecules will be summarized, and their relevance for pulmonary structure and inflammation will be discussed.

Animals↗

PubMed1993

Distribution of integrin cell adhesion receptors on normal bronchial epithelial cells and lung cancer cells in vitro and in vivo.

The interactions of bronchial epithelial cells with the basement membrane control cell morphology, differentiation, and proliferation in addition to having a major role in malignant transformation. Since these interactions are mediated by the integrin family of cell adhesion receptors, we characterized the integrin repertoire and adhesive properties of normal human bronchial epithelial cells in culture and cell lines derived from nine lung carcinomas using subunit-specific monoclonal antibodies. In addition, the integrin repertoire of three of the transformed cell lines was reexamined after the cells formed tumor nodules in immunodeficient mice. Bronchial epithelial cells in culture expressed multiple integrin subunits with the capability of binding to collagen and laminin (alpha 2, alpha 3, and alpha 6) and at least two subunits that are capable of mediating adhesion to fibronectin (alpha 3 and an alpha v-containing integrin). The alpha v beta 3 vitronectin receptor was not present. This distribution closely mimicked that seen by bronchial epithelial cells in situ. Cell lines derived from transformed pulmonary epithelial cells showed great heterogeneity with respect to integrin expression--some showing fewer, some greater, and some the same types of integrins as nontransformed epithelial cells. Only slight changes in integrin expression were seen in tumor cells propagated in immunodeficient mice. Although the adhesion characteristics of the transformed cells mirrored their adhesion receptor profile, no correlation between integrin profile and the ability to grow in SCID mice was observed. This study defines the integrin repertoire of human bronchial epithelial cells and sets the stage for future investigations exploring how the regulation and signal transduction mechanisms of these receptors might affect important pulmonary processes such as bronchial cell differentiation, wound healing, and malignant transformation.

Animals↗

PubMed1993

Human/severe combined immunodeficient mouse chimeras. An experimental in vivo model system to study the regulation of human endothelial cell-leukocyte adhesion molecules.

The ability of circulating white blood cells to enter inflamed tissues is mediated by specific cell adhesion molecules thought to be expressed in a programmed and sequential manner to form an "adhesion cascade." Because of the complexity of this process, it is becoming increasingly important to develop in vivo models. Two major problems have limited the utility of current animal models. The first is the inability of many of the antibodies developed against cell adhesion molecules in human cell culture models to cross-react in animals. The second is the uncertainty in extrapolating animal (particularly rodent) findings to humans. To circumvent these problems, full thickness human skin grafts were transplanted onto immunodeficient (severe combined immunodeficient) mice. After 4-6 wk, the transplanted skin grafts closely resembled normal skin histologically and maintained their human vasculature as determined by immunohistochemical staining with human-specific endothelial cell markers. Intradermal injection of tumor necrosis factor-alpha resulted in the reversible upregulation of the leukocyte-endothelial adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1, and in an active inflammatory reaction with migration of murine leukocytes into cytokine-injected areas. These results indicate that the severe combined immunodeficient mouse/human skin transplant model provides a useful in vivo system in which to study human endothelium during the process of inflammation.

Adult↗

PubMed1993

Regulation of extracellular matrix proteins and integrin cell substratum adhesion receptors on epithelium during cutaneous human wound healing in vivo.

Although changes in extracellular matrix proteins during wound healing have been well documented, little is known about the regulation of corresponding extracellular matrix adhesion receptors (integrins). To study this process in a human in vivo model, full thickness human skin grafts were transplanted onto severe combined immunodeficient mice and deep excisional wounds involving both the epidermal and dermal layers were then made. The changes in the expression of cell matrix proteins and epithelial integrins over time were analyzed with specific antibodies using immunohistochemistry. Wounding was associated with alterations in extracellular matrix proteins, namely, loss of laminin and type IV collagen in the region of the wound and expression of tenascin and fibronectin. Changes were also noted in the integrins on the migrating keratinocytes. There was marked up-regulation of the alpha v subunit and de novo expression of the fibronectin receptor (alpha 5 beta 1) during the stage of active migration (days 1 to 3 after wounding). In the later stages of wound healing, after epithelial integrity had been established, redistribution of the alpha 2, alpha 3, alpha 6, and beta 4 collagen/laminin-binding integrin subunits to suprabasal epidermal layers was noted. Thus, during cutaneous wound healing, keratinocytes up-regulate fibronectin/fibrinogen-binding integrins and redistribute collagen/laminin-binding integrins. This study demonstrates that the human skin/severe combined immunodeficient chimera provides a useful model to study events during human wound repair.

Animals↗

PubMed1993

Cell adhesion receptors and early mammalian heart development: an overview.

Cardiovascular development is the end result of a complex genetic program subject to regulation by signals transmitted between a cell and its extracellular environment. As cells encounter new extracellular matrices or establish new cell-cell interactions, new genes must be activated to accommodate the altered developmental situation within which the cell finds itself. This is likely reflected in a program of adhesion receptor and counter receptor expression on the surface of cells engaged in the morphogenesis. To understand the molecular basis of development, it is necessary to first determine if such a program exists and then to establish the role of various receptors and counter receptors in the particular morphogenetic process under investigation. To this end, we have initiated an investigation into expression of specific adhesion receptors during cardiovascular development in the mouse. Here, we demonstrate that platelet endothelial cell adhesion molecule (PECAM)-1 is an excellent marker for following vascular formation in the mammalian embryo. It is expressed during development in several alternatively spliced forms involving the cytoplasmic domain of the molecule. These forms differ in their ligand binding properties. Thus, a change in the cytoplasmic domain affects the folding of the molecule in such a way as to structurally alter the extracellular domain. Further, several receptors including the laminin receptor, the fibronectin receptor and a hyaluronic acid receptor, display specific expression patterns during heart development. These include differential expression in the endocardium and myocardium, down regulation during endocardial and myocardium, down regulation during endocardial cushion formation and cessation of expression in particular regions of the heart upon maturation. Interference with the function of one of these receptors (the fibronectin receptor) results in aberrant heart formation. These observations strongly support the concept that morphogenesis requires specific cell adhesion molecules that are expressed in precisely choreographed programs.

Animals↗

PubMed1993

Growth and invasion of human melanomas in human skin grafted to immunodeficient mice.

An orthotopic model of human melanoma was developed in which malignant cells were injected into human skin grafted to nude and SCID mice. Melanoma cells proliferated and invaded the human skin grafts with characteristic patterns. Three of six melanomas grew as multiple nodules and infiltered the grafts without major architectural changes in the dermis, whereas the others invaded the dermis along collagen fibers with prominent endothelial vessels. By contrast, melanoma cells inoculated into mouse skin grew as diffusely expanding nodules that did not invade the murine dermis. In human skin grafts, human melanoma cells were angiogenic for human blood vessels, and murine vessels were only found at the periphery of grafts. Tumor cells invaded the human vessels, and four out of seven cell lines metastasized to lungs, suggesting that this model is useful to determine in vivo the interactions between normal and malignant human cells.

Animals↗

PubMed1993

Role of integrins and other cell adhesion molecules in tumor progression and metastasis.

Despite rapid advances in our understanding of the biology of cell adhesion, the data available in the literature make it is difficult to propose one simple scheme in which cell adhesion molecules can be related to tumor growth and metastasis. This difficulty can be related to a number of factors. Some of the apparently conflicting experimental results that demonstrate both enhanced or diminished tumor cell adhesion during tumor progression may be attributed to the experimental systems used. Those studies that have injected tumor cells intravenously have, in general, shown that enhanced tumor cell adhesiveness correlates with metastatic ability. It should be recognized that this experimental approach bypasses many of the early stages of the metastatic cascade and is biased towards tumor cells with an enhanced ability to form aggregates with cells in the circulation and to adhere to distant vascular sites. On the other hand, studies that have implanted tumors into animals and allowed them to grow and metastasize (spontaneous metastasis) have generally demonstrated an inverse relationship between adhesive ability and the ability to metastasize. Another major obstacle in understanding the role of CAMs in metastasis is the well known problem of tumor heterogeneity and the phenotypic instability of metastatic cells over relatively short periods of time (141). The cells that make up a metastatic focus may thus be quite different from the tumor cells that originally formed the lesion. It is quite possible that the selective pressures that initially enable a cancer cell to form a metastatic lesion may be quite different than those that later favor rapid tissue growth. The major obstacle in making any sweeping generalizations about cell adhesion molecules and tumor progression, however, is that the process of successful metastasis is inherently complex, requiring tumor cells to possess decreased adhesive interactions with surrounding cells and extracellular matrix at some points in the cascade and increased adhesive interactions at other times. Based on the information available, the following scenario can be proposed. Using the schema shown in Figure 1, successful metastasis initially requires that normal cell-cell and cell-substratum adhesion be disrupted, causing release of neoplastic cells from the primary tumor (step 1). For epithelial tumors, down-regulation of cadherins and perhaps, integrins, appear to be involved. This loss of cell adhesion must be followed by migration of tumor cells into the vascular system (step 2), a step requiring efficient cell-substratum interactions. In melanomas, this step seems to require expression of the vitronectin receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta 1 integrin-mediated adhesion.

The CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]/endothelial cell adhesion molecule [endoCAM]) molecule expressed on leukocytes, platelets, and endothelial cells is postulated to mediate adhesion to endothelial cells and thereby function in immunity, inflammation, and wound healing. We report the following novel features of CD31 which suggests a role for it in adhesion amplification of unique T cell subsets: (a) engagement of CD31 induces the adhesive function of beta 1 and beta 2 integrins; (b) adhesion induction by CD31 immunoglobulin G (IgG) monoclonal antibodies (mAbs) is sensitive, requiring only bivalent mAb; (c) CD31 mAb induces adhesion rapidly, but it is transient; (d) unique subsets of CD4+ and CD8+ T cells express CD31, including all naive (CD45RA+) CD8 T cells; and (e) CD31 induction is selective, inducing adhesive function of beta 1 integrins, particularly very late antigen-4, more efficiently than the beta 2 integrin lymphocyte function-associated antigen-1. Conversely, CD3 is more effective in inducing beta 2-mediated adhesion. Taken together, these findings indicate that unique T cell subsets express CD31, and CD31 has the capacity to induce integrin-mediated adhesion of T cells in a sensitive and selective fashion. We propose that, in collaboration with other receptors/ligands, CD31 functions in an "adhesion cascade" by amplifying integrin-mediated adhesion of CD31+ T cells to other cells, particularly endothelial cells.

Antibodies, Monoclonal↗

PubMed1992

A heterophilic adhesion mechanism for platelet/endothelial cell adhesion molecule 1 (CD31).

The molecular nature of cell adhesion mediated by platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) was examined using stably transfected L cells in a PECAM-dependent aggregation assay. This adhesion was temperature sensitive and divalent cation dependent, with Mg2+ supporting aggregation to a greater degree than Ca2+. PECAM-dependent aggregation was heterophilic: PECAM-1 transfectants bound as readily to control-transfected L cells as to other PECAM-1 transfectants, demonstrating that a molecule endogenously expressed on the L cells serves as the ligand for PECAM in this system and presumably substitutes for the natural human ligand.

Animals↗

PubMed1992

Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration.

Cell migration is an important process in such phenomena as growth, development, and wound healing. The control of cell migration is orchestrated in part by cell surface adhesion molecules. These molecules fall into two major categories: those that bind to extracellular matrix and those that bind to adjacent cells. Here, we report on the role of a cell-cell adhesion molecule, platelet-endothelial cell adhesion molecule-1, (PECAM-1), a member of the lg superfamily, in the modulation of cell migration and cell-cell adhesion. PECAM-1 is a 120-130 kDa integral membrane protein that resides on endothelial cells and localizes at sites of cell-cell contact. Since endothelial cells express PECAM-1 constitutively, we studied the effects of PECAM-1 on cell-cell adhesion and migration in a null-cell population. Specifically, we transfected NIH/3T3 cells with the full length PECAM-1 molecule (two independent clones). Transfected cells containing only the neomycin resistance gene, cells expressing a construct coding for the extracellular domain of the molecule, and cells expressing the neu oncogene were used as controls. The PECAM-1 transfectants appeared smaller and more polygonal and tended to grow in clusters. Indirect immunofluorescence of PECAM-1 transfectants showed peripheral staining at sites of cell-cell contact, while the extracellular domain transfectants and the control cells did not. In two quantitative migration assays, the full-length PECAM-1 transfectants migrated more slowly than control cells. Thus, PECAM-1 transfected into a null cell appears to localize to sites of cell-cell contact, promote cell-cell adhesion, and diminish the rate of migration. These findings suggest a role for this cell-cell adhesion molecule in the process of endothelial cell migration.

Animals↗

PubMed1992

Identification of integrin cell-substratum adhesion receptors on cultured rat bone cells.

The interactions of bone cells with their extracellular matrix is of major importance in bone development, repair, and disease. We examined the ability of rat calvarial bone cells to adhere to various matrix proteins and to define the role of integrin cell-substrate adhesion receptors in these interactions. Isolated newborn rat calvarial bone cells prelabeled with 3H-thymidine and plated on plastic wells that had been precoated with serial dilutions of various substrates showed typical dose-response adherence curves to fibronectin, fibrinogen, laminin, vitronectin, and collagen I and IV. Cell adherence to poly-D-lysine, a nonspecific cell adherent, was high at all substrate concentrations > 0.0001 micrograms/ml. A polyclonal anti-rat integrin antibody blocked cell adhesion to all substrates tested except poly-D-lysine. Isolated rat calvarial bone cells were surface labeled with 125I, extracted, and immunoprecipitated with polyclonal antibodies made against the rat integrin complex and peptides derived from the cytoplasmic domains of the alpha 2, alpha 3, and alpha 5 subunits. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (nonreduced) identified four bands representing a mixture of integrins including the alpha 1 beta 1 laminin/collagen receptor, the alpha 5 beta 1 fibronectin receptor, and the alpha V beta 3 (or possibly alpha V beta 5) vitronectin receptor. These experiments show that bone cells adhere to a wide variety of extracellular matrix proteins via specific integrins. Increased knowledge about the regulation of these receptors and the mechanisms by which they transmit information to the cell will be important for a more complete understanding of bone physiology and pathophysiology.

Animals↗

PubMed1992

Differential expression of integrin cell-substratum adhesion receptors on endothelium.

The interactions of the endothelial cells with their underlying extracellular matrix is of fundamental importance to angiogenesis. Therefore, the distribution of integrin cell-substratum adhesion receptors on cultured and in situ endothelial cells was determined. Cultured endothelium from large and small vessels and large vessel endothelial cells in situ expressed integrins that bound to both basement membrane and inflammatory matrix components. In contrast, in situ microvessels primarily expressed basement membrane binding integrins. Alterations in the expression of the integrins on microvessel endothelial cells may be important for microvascular remodeling during wound healing and/or angiogenesis.

Antibodies, Monoclonal↗

PubMed1992

Cytokine-induced expression of transforming growth factor-alpha and the epidermal growth factor receptor in neonatal skin explants.

Hyperproliferative diseases of the epidermal keratinocytes, such as psoriasis vulgaris, are characterized by overexpression and altered distribution of the epidermal growth factor/transforming growth factor (EGF/TGF)-alpha receptor, and of TGF-alpha itself. It is believed that overexpression of this lignad/receptor system contributes to the hyperproliferative state of keratinocytes in an autocrine fashion. However, little is known about the factors that regulate expression of the EGF/TGF-alpha receptor, as well as expression of TGF-alpha in stratified epithelium. We examined modulation of the immunoreactive EGF/TGF-alpha receptor and TGF-alpha expression in normal neonatal foreskin explants by a variety of cytokines present in psoriatic lesions. Human (hu) recombinant (r) tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma induced EGF/TGF-alpha receptor and TGF-alpha expression by keratinocytes as determined by immunohistochemistry. Neutralizing antibodies to TNF-alpha and IFN-gamma inhibited upregulation of EGF/TGF-alpha receptors and TGF-alpha by the respective cytokines. Interleukin (IL)-8 induced expression of TGF-alpha, but not of its receptor. Other cytokines (TNF-beta, IFN-beta, IL-1 alpha, IL-2, IL-3, IL-5, IL-6, granulocyte/macrophage colony-stimulating factor, and macrophage colony-stimulating factor) did not alter the expression patterns of EGF/TGF-alpha receptors or TGF-alpha in normal neonatal skin explants. These experiments demonstrate that specific cytokines known to be present in psoriatic lesions can induce normal epidermis to express TGF-alpha and its receptor in a pattern similar to that observed in psoriatic skin.

Cytokines↗

PubMed1992

Distribution of integrin cell adhesion receptors in normal and malignant lung tissue.

The integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular morphology, differentiation, and proliferation. The integrin repertoire of a cell may therefore influence its behavior under resting conditions or following malignant transformation. For this reason, the distribution of integrins in normal lung tissues was determined using monoclonal antibodies against integrins of the beta 1 (VLA) and beta 3 (cytoadhesin) subfamilies and compared with the distribution in a limited number of lung carcinomas. The integrin subunits that bind to collagen and laminin (alpha 1, alpha 2, alpha 3, and alpha 6) and the alpha subunit, which can pair with beta 1, beta 3, or beta 5 and promote fibronectin, fibrinogen, or vitronectin binding, were the predominant integrins expressed on the major cell types of the lung, i.e., bronchial epithelium, vascular endothelium, and smooth muscle. Strong expression of the alpha 5 beta 1 fibronectin receptor and the beta 3 subunit was restricted to the endothelium of large vessels. Integrin expression by the lung carcinoma cells was somewhat heterogeneous; however, the tumors tended to express fewer integrins than did the normal bronchial epithelium.

Cell Adhesion↗

PubMed1992

Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle.

Integrins are a class of cell adhesion molecules that participate in cell-cell and cell-substratum interactions and are present on essentially all human cells. The distribution of nine different alpha and beta integrin subunits in human endometrial tissue at different stages of the menstrual cycle was determined using immunoperoxidase staining. Glandular epithelial cells expressed primarily alpha 2, alpha 3, and alpha 6 (collagen/laminin receptors), while stromal cells expressed predominantly alpha 5 (fibronectin receptor). The presence of alpha 1 on glandular epithelial cells was cycle specific, found only during the secretory phase. Expression of both subunits of the vitronectin receptor, alpha v beta 3, also underwent cycle specific changes on endometrial epithelial cells. Immunostaining for alpha v increased throughout the menstrual cycle, while the beta 3 subunit appeared abruptly on cycle day 20 on luminal as well as glandular epithelial cells. Discordant luteal phase biopsies (greater than or equal to 3 d "out of phase") from infertility patients exhibited delayed epithelial beta 3 immunostaining. These results demonstrate similarities, as well as specific differences, between endometrium and other epithelial tissues. Certain integrin moieties appear to be regulated within the cycling endometrium and disruption of integrin expression may be associated with decreased uterine receptivity and infertility.

Adult↗

PubMed1992

Cellular and molecular aspects of PECAM-1.

PECAM-1 is a surface membrane glycoprotein of 130,000 daltons found on platelets, endothelial cells, monocytes, neutrophils, and certain T-cell subsets. Except for bone marrow precursor cells, it does not seem to be found outside the vasculature. Previous studies have shown that PECAM-1 is a member of the immunoglobulin gene superfamily that localizes to the intercellular junction in cells, like endothelial cells, that grow in monolayers. We and other laboratories have been involved in studies designed to define the role of PECAM-1 in various cell types. Mammalian expression vectors have been constructed that express all, or selected domains, of the PECAM-1 protein. These vectors have been used to induce PECAM-1 expression in a variety of both monolayer and suspension cell types. Domain-specific anti-PECAM-1 monoclonal antibodies, synthetic peptides, and heparin were also used to define structurally and functionally important domains of this membrane glycoprotein. Protein synthesis, subcellular localization, and association with the cytoskeletons of various cells expressing PECAM-1 were examined. From these studies we have obtained evidence that: (1) PECAM-1 redistributes to the border of monolayer cells when they contact each other. (2) Border localization may result from homophilic interactions, i.e. PECAM-1 on one cell binds PECAM-1 on the adjacent cell. (3) Suspension cells such as L-cells or neutrophils may also interact via PECAM-1 mediated interactions, but an as yet unidentified ligand probably participates in a heterophilic, rather than homophilic, type of interaction. (4) Intracellular movement of PECAM-1 in both monolayer and suspension cell types requires active participation of the cytoskeleton.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗