Intercellular Adhesion Molecule-1 Immunoreactivity Research Articles

Over-expression of ICAM-1, VCAM-1 and ELAM-1 might influence tumor progression in colorectal cancer.

Adhesion molecules might play a role in tumor progression. We investigated expression of the adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in 24 primary colorectal carcinomas using immuno-histochemistry and Northern blot analysis. Normal colonic tissue from the same patients served as controls. ICAM-1 immunostaining was restricted to the intercellular matrix and vascular endothelial cells. The vast majority of normal tissue samples revealed only faint ICAM-1 immunoreactivity. However, moderate to strong immunostaining was found in 86% of cancerous sections. The ICAM-1 immunoreaction was more intense in well-differentiated carcinomas as well as in the adenomatous parts and transition zones of cancers. Similarly, the cancers exhibited markedly enhanced VCAM-1 and ELAM-1 immunostaining in the endothelial cells of small blood vessels. The intense vascular immunostaining by ICAM-1 and VCAM-1 was associated with a strong presence of CD3-positive T lymphocytes, whereas ELAM-1 immunoreactivity did not correlate with round cell infiltration. On Northern blot analysis, ICAM-1, VCAM-1 and ELAM-1 mRNA levels were increased in 67%, 57% and 63% of carcinomas, respectively, in comparison with normal tissue samples. Densitometric analysis of Northern blots revealed an increase in ICAM-1 by 2.1-fold, an increase in VCAM-1 by 3.4-fold and an increase in ELAM-1 by 2.2-fold in cancerous tissues compared to normal controls. Over-expression of ICAM-I might prevent cell-cell disruption and, hence, tumor dissemination. Furthermore, over-expression of ICAM-1 and VCAM-1, but not ELAM-1, might favor host anti-tumor defense by trafficking of lymphocytes.

Over‐expression of ICAM‐1, VCAM‐1 and ELAM‐1 might influence tumor progression in colorectal cancer

Adhesion molecules might play a role in tumor progression. We investigated expression of the adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in 24 primary colorectal carcinomas using immuno-histochemistry and Northern blot analysis. Normal colonic tissue from the same patients served as controls. ICAM-1 immunostaining was restricted to the intercellular matrix and vascular endothelial cells. The vast majority of normal tissue samples revealed only faint ICAM-1 immunoreactivity. However, moderate to strong immunostaining was found in 86% of cancerous sections. The ICAM-1 immunoreaction was more intense in well-differentiated carcinomas as well as in the adenomatous parts and transition zones of cancers. Similarly, the cancers exhibited markedly enhanced VCAM-1 and ELAM-1 immunostaining in the endothelial cells of small blood vessels. The intense vascular immunostaining by ICAM-1 and VCAM-1 was associated with a strong presence of CD3-positive T lymphocytes, whereas ELAM-1 immunoreactivity did not correlate with round cell infiltration. On Northern blot analysis, ICAM-1, VCAM-1 and ELAM-1 mRNA levels were increased in 67%, 57% and 63% of carcinomas, respectively, in comparison with normal tissue samples. Densitometric analysis of Northern blots revealed an increase in ICAM-1 by 2.1-fold, an increase in VCAM-1 by 3.4-fold and an increase in ELAM-1 by 2.2-fold in cancerous tissues compared to normal controls. Over-expression of ICAM-1 might prevent cell–cell disruption and, hence, tumor dissemination. Furthermore, over-expression of ICAM-1 and VCAM-1, but not ELAM-1, might favor host anti-tumor defense by trafficking of lymphocytes. Int. J. Cancer (Pred. Oncol.) 79:76–81, 1998. © 1998 Wiley-Liss, Inc.

Adhesion Molecules and Microvascular Changes in the Nonobese Diabetic (NOD) Mouse Pancreas. An NO-Inhibitor (L-Name) is Unable to Block Adhesion Inflammation-Induced Activation

The aim of the present study was to investigate the immunoreactivity of pancreatic microvasculature with emphasis on the adhesion molecule expression in NOD mice at a very early stage and after the start of infiltration, before the onset of the diabetic disease. Immunoreactivity for Ia-b, BM8 (mouse macrophages) and inter-cellular-adhesion-molecule-1 (ICAM-1) molecules in untreated control mice and in animals treated using an inhibitor of nitric oxide (NO) formation (L-arginine analogue), as well as islet culture, nitrite assay and ultrastructural studies were performed. Results showed that Ia-b and ICAM-1 immunoreactivities on endothelia are a very early phenomenon and that pancreatic blood vessels and, in particular, some peri-islet venules, as well as several venules of the exocrine parenchyma, undergo significant morphological changes. Several endothelial cells of both peri-islet and extra-islet compartments, often showed Ia-b and ICAM-1 immunoreactivities, demonstrating that these cells are important for the adhesion processes taking place during early autoimmune inflammation. Inhibition of NO formation does not significantly affect ICAM-1 and Ia-b immunoreactivity both in vivo and in vitro, BM8 immunoreactive cells were considerably less in number although these were detected either around islets or along pancreatic septa, but rarely within the epithelial layer.

Intercellular adhesion molecule-1 (ICAM-1) in the mouse facial motor nucleus after axonal injury and during regeneration.

Intercellular adhesion molecule 1 (ICAM-1, CD54) is a widely expressed glycoprotein, which plays an important role in leukocyte extravasation and in the interaction of lymphocytes with antigen-presenting cells. In the current study we examined the regulation of ICAM-1 in the mouse facial motor nucleus after facial nerve transection, using immunohistochemistry, confocal laser microscopy and electron microscopy. In the normal facial nucleus ICAM-1 immunoreactivity was restricted to vascular endothelium. Transection of the facial nerve led to a strong and selective upregulation of ICAM-1 on activated microglia. Quantitation of microglial ICAM-1 immunoreactivity revealed a biphasic increase. The first peak 1-2 days post operation paralleling the early stage of microglial activation was followed by a decline at 4-7 days. The second induction of ICAM-1 occurred at day 14 accompanying the period of neuronal cell death and microglial phagocytosis of neuronal debris. Immunoelectron microscopy showed strong ICAM-1 reactivity on the cell membrane of activated microglia at day 2. During the second peak (day 14), ICAM-1 was also observed on lymphocytes adhering to phagocytotic microglia forming aggregates around neuronal debris. No immunolabelling was observed on neurons, astrocytes or oligodendroglia. These data suggest the involvement of ICAM-1 in the adhesion of activated microglia, in their phagocytosis of neuronal debris, and also in the interaction with infiltrating lymphocytes following this injury.

Expression of LFA-1α and ICAM-1 in the developing rat brain: a potential mechanism for the recruitment of microglial cell precursors

Several studies agree that microglial cells derive from monocytes that infiltrate the central nervous system during development, but the precise mechanism by which these cells enter into the nervous tissue is still unknown. In this way, the aim of the present study was to analyze the expression of two cell adhesion molecules involved in the recruitment of blood leukocytes into tissues, the lymphocyte function-associated antigen-1α (LFA-1α) and the intercellular adhesion molecule-1 (ICAM-1) in the developing rat brain (from E16 to P18). By means of immunohistochemistry, our observations showed that LFA-1α and ICAM-1 were expressed in the developing rat brain with a definite distribution pattern and a characteristic time course of appearance. In the embryonic period, LFA-1α immunoreactivity was displayed not only by intravascular blood cells but also by intraparenchymal round cells with a horseshoe-shaped nucleus, showing the typical morphological features of monocytes. Monocyte-like cells present in the embryonic brain parenchyma often displayed mitotic profiles. LFA-1α immunohistochemistry also revealed the presence of some LFA-1α-positive cells belonging to the ameboid microglial population (mostly in the white matter from E18). In the postnatal period, LFA-1α immunoreactivity was displayed by some ameboid microglial cells (P0–P9) and also by some ramified microglia. LFA-1α immunoreactivity observed in ramified microglia was weaker when compared to LFA-1α stained ameboid microglia. In contrast, ICAM-1 immunolabeling during the embryonic period was mainly located in endothelial cells of parenchymal brain blood vessels (principally from day E18). Blood vessels in choroid plexus and meninges also expressed ICAM-1 during the embryonic time. In postnatal animals, ICAM-1 immunoreactivity was found in relation to endothelial cells of blood vessels, but the density of ICAM-1-positive blood vessels was lower than that during the embryonic period. The gradual regulation in the expression of LFA-1α by monocyte-like cells and cells of the microglial lineage, and the expression of ICAM-1 by the brain vasculature strongly suggest that the LFA-1/ICAM-1 system may be a mechanism involved in the entry of microglial cell precursors into the developing rat brain.

Endothelial cell expression of intercellular adhesion molecule 1 in experimental posthemorrhagic vasospasm.

The exposure of large intracranial arteries to blood after an aneurysmal subarachnoid hemorrhage leads to a cascade of morphological and physiological changes in the vessels, a condition generally described as vasospasm. This response to the periadventitial deposition of blood is mediated in part by the endothelial layer of the vessel. This study was undertaken to examine the role of endothelial cell expression of intercellular adhesion molecule 1 (ICAM-1) in the initiation and regulation of this response. The femoral artery model of vasospasm was used in rats (65 animals, 130 arteries). In each rat, one artery was exposed to blood and the contralateral vessel was exposed to saline, so that each animal served as its own control. Animals were perfused and killed at sequential time points, from 1 hour to 20 days after blood exposure. The vessels were examined immunohistochemically and histologically for the presence of ICAM-1 and morphological features of vasospasm, respectively. Endothelial cell ICAM-1 immunoreactivity was extensively increased in only the blood-exposed vessels, beginning 3 hours after clot placement and persisting for 24 hours. ICAM-1 immunoreactivity returned to baseline by 48 hours after blood exposure. The influx of inflammatory cells correlated directly with the time and location of increased ICAM-1 expression. Peak arterial remodeling was observed on the blood-exposed side 8 to 12 days after clot placement, as quantified by measurements of increased wall thickness, decreased lumen size, and increased collagen content. Endothelial cell ICAM-1 expression seems to be an early and specific signal used by a vessel in response to the deposition of blood periadventitially. This molecule may be a marker for vessels likely to undergo subsequent morphological remodeling and vasospasm.

Distribution of Immunoglobulin Superfamily Members ICAM-1, -2, -3, and the β2 Integrin LFA-1 in Multiple Sclerosis Lesions

To identify potential molecular substrates for leukocyte trafficking and activation in multiple sclerosis (MS) brain, we determined the immunocytochemical distribution of the beta, integrin lymphocyte-function-associated antigen-1 (LFA-1) and its major ligands, intercellular adhesion molecule (ICAM)-1, ICAM-2, and ICAM-3 in MS tissue. Colocalization of these adhesion molecules with lineage-specific markers was analyzed by dual-labeling immunocytochemistry and confocal microscopy. ICAM-1 and ICAM-2 were detected on endothelial cells, and ICAM-3 immunoreactivity was restricted to infiltrating leukocytes. In control brain, 10% of glucose transporter-1 positive vessels contained ICAM-1 immunoreactivity on their luminal surface and 21% were ICAM-2-positive. A significant increase in ICAM-1-positive vessels was found in MS brains. This increase was greater in MS lesions (81% of vessels) than in nonlesion areas (37% of vessels). A significant increase in ICAM-1-positive vessels was found in encephalitis (55% of vessels) but not in Parkinson's (17% of vessels) brains. The percentage of vessels expressing ICAM-2 was not increased in MS, encephalitis, or Parkinson's brains. Both ICAM-3 and LFA-1 were detected on the vast majority of infiltrating lymphocytes and monocytes in and near MS lesions, and these cells were often closely apposed to each other. In addition, LFA-1 was detected on activated microglia located close to the edge of demyelinating lesions. ICAM-3-positive leukocytes were often closely apposed to LFA-1-positive microglia. These results suggest a role for ICAM-1, -2, and LFA-1 in the transendothelial migration of leukocytes into MS brain and a role for ICAM 3/LFA-1 interactions in the activation of lymphocytes, monocytes, and microglia in MS lesions.

Changes in adhesion molecule expression during distinct patterns of immune cell migration in the inflamed lung.

In response to antigen inhalation, immune cells including alveolar macrophages expressing a VIP1 receptor subtype (VIP1R), lymphocytes and leukocytes participate in the inflammatory event, migrating into and from vascular regions in lung tissue of sensitized mice. To analyze these migratory mechanisms of immune cells, we immunohistochemically examined the expression of the following: cellular adhesion molecules, lymphocyte function-associated antigen-1 (LFA-1) very late activation antigen-4 (VLA-4), and the alpha V (alpha v) subunit and their respective ligands, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and fibronectine; the examination was carried out in pulmonary tissue from days 0, 2, 6 and 12 following intratracheal administration of sheep red blood cells (SRBC) as an antigen to previously sensitized mice. Two days following the antigen challenge, VIP1R-positive macrophages strongly expressing the alpha v integrin subunit were found clustered on the endothelial surface and among the aggregates of perivascularly infiltrated leukocytes. On the endothelium of arteries, veins and capillaries, alpha v immunoreactivity was prominently reduced, whereas staining for fibronectin was enhanced more than the prechallenge control level. The blood vessel endothelium was also stained positive for VCAM-1 and ICAM-1, while many of the infiltrating lymphocytes were positive for VLA-4 and LFA-1 immunolabelings. By post-challenge, day 6, delta v integrin subunit immunoreactivity was re-expressed on the blood vessel endothelium and only weakly expressed on VIP1R-positive macrophages, which were in retreat from the leukocyte-aggregating perivascular region and located in the alveoli. VLA-4 bearing lymphocytes conspicuously increased in number among the perivascular leukocytes, while immunoreactivity for LFA-1, VCAM-1, ICAM-1 and fibronectin was unchanged from that for post-challenge day 2. The results indicate that the expression of the alpha v-bearing integrin and its ligand fibronectin drastically changes as pulmonary inflammatory responses. These changes in expression of adhesion molecules during immune response may play an important role in the dynamic regulation of VIP1R-positive macrophage migration in the lung parenchymal compartment.

Characterization of adhesion receptors on cultured microvascular endothelial cells derived from the retroorbital connective tissue of patients with Graves' ophthalmopathy

T lymphocytes have been demonstrated recently to play an important role in the pathogenesis and propagation of Graves' ophthalmopathy (GO). Recruitment of T cells to the retroorbital tissue in GO involves the activation of certain adhesion molecules both in the vascular endothelium and in the extravascular connective tissue within the retroorbital space. To characterize the interactions between orbital endothelial cells (OECs) and circulating T cells in vitro, we discussed a two-step immunopurification procedure with bead-immobilized Ulex europaeus I lectin and anti-human endothelial cell antigen (CD31) monoclonal antibody for rapid and reproducible isolation of highly pure microvascular endothelial cell populations from small quantities of retroorbital connective tissue. Endothelial origin of the resulting cell populations was confirmed by positive immunoreactivity for von Willebrand factor. CD31 and thrombomodulin. Under baseline conditions, GO-OECs, but not normal OECs, expressed intercellular adhesion molecule 1 (ICAM-1) and CD44 immunoreactivity but no immunoreactivity for endothelial leukocyte adhesion molecule 1 (ELAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was detected. Exposure of GO-OEC and normal OEC monolayers to interferon gamma, interleukin 1 alpha and tumor necrosis factor alpha resulted in marked up-regulation of immunoreactivity for ICAM-1 and in induction of ELAM-1 and VCAM-1. Blocking experiments using monoclonal antibodies directed against various adhesion molecules demonstrated that interactions between matched activated T lymphocytes and OECs were mediated by integrin-dependent (ICAM-1/leukocyte function-associated antigen 1 (LFA-1): VCAM-1/very late antigen 4 (VLA-4)) and integrin-independent (CD44) pathways, and revealed marked differences when comparing GO-OECs and normal OECs. In conclusion, the availability of OECs from affected retroorbital tissue of patients with GO provides a valuable tool for studying further the mechanisms responsible for orbit-specific lymphocyte recruitment in GO.

Immunohistochemical evidence for loss of ICAM-1 by alveolar epithelial cells in pulmonary fibrosis.

ICAM-1 is an intercellular adhesion molecule of the immunoglobulin supergene family involved in adherence of leukocytes to the endothelium and in leukocytic accumulation in pulmonary injury. In the current study, the antigen retrieval technique was used to detect ICAM-1 immunohistochemically in paraffin sections of lungs from human, mouse and rat as well as in bleomycin- or radiation-induced fibrotic lungs from rat and human. In normal lung tissue, the expression of ICAM-1 on alveolar type I epithelial cells is stronger than on alveolar macrophages and on endothelial cells. Preembedding immunoelectron microscopy of normal rat, mouse and human lung samples revealed selective ICAM-1 expression on the surface of type I alveolar epithelial cells and, to a lesser extent, on the pulmonary capillary endothelium and on alveolar macrophages. In fibrotic specimens, both focal lack and strengthening of immunostaining on the surface of type I cells was found. Alveolar macrophages were found focally lacking ICAM-1 immunoreactivity. In some cases, rat type II pneumocytes exhibited positive immunoreactions for ICAM-1. Immunoelectron microscopy with preembedded rat lungs (bleomycin-exposed cases) confirmed the altered ICAM-1 distribution at the alveolar epithelial surface. In the alveolar fluid of fibrotic rat lungs, in contrast to that from untreated controls, soluble ICAM-1 was detected by western blot analysis.

Lymphocytic Infiltration and Expression of Intercellular Adhesion Molecule-1 in Photochemically Induced Ischemia of the Rat Cortex

The contribution of the immune system to the pathogenesis of ischemic lesions is still uncertain. We have analyzed leukocyte infiltration in photochemically induced focal ischemia of the rat parietal cortex by immunocytochemistry. Between 1 and 2 days after photothrombosis, CD5+ T cells adhered to subpial and cortical vessels and infiltrated the ischemic lesion prior to macrophages. By day 3 numerous T cells and some macrophages, whose number increased further between day 3 and day 7, had infiltrated the border zone around the lesion sparing the center. In addition, CD5-/CD8+ lymphocytes that probably represent natural killer cells were found. Intercellular adhesion molecule-1 (ICAM-1) was expressed on endothelial cells on days 1 and 2 and in the border zone on infiltrating leukocytes from day 3 to day 7. Starting on day 7, macrophages infiltrated the core of the lesion to remove debris. When the entire lesion was covered by macrophages at day 14, the number of T cells had decreased and ICAM-1 immunoreactivity was no longer found in or around the infarct. In conclusion, our study shows that ischemic lesions can lead to a local immune reaction in the CNS. Thus, blocking of lymphocyte-derived cytokines or cell adhesion molecules may provide a new approach to confining the sequelae of stroke.

Increased immunoreactive rat lung ICAM-1 in oleic acid-induced lung injury.

Levels of immunoreactive ICAM-1 in rat lung were followed during the kinetic development of acute oleic acid-induced lung injury in the rat by the ELISA assay. Significant increases in ICAM-1 immunoreactivity were found on rat lung membranes within 30 min of oleic acid injection. The increased immunoreactive ICAM-1 persisted for the duration of the study (4 h) and paralleled lung injury as measured by decreased lung compliance. Enhanced ICAM-1 immunofluorescence was also observed on cryostat sections of lungs from oleic acid-treated rats. No direct effect of oleic acid on ICAM-1 levels of cultured human umbilical vein endothelial cells or rat lung microvascular endothelial cells was observed. This suggests that either oleic acid raises rat lung ICAM-1 levels on endothelial cells by an indirect mechanism or that oleic acid increases ICAM-1 levels on other cell types, such as fibroblasts or lung epithelial cells, by direct or indirect mechanisms. Some of the increased ICAM-1 may also be due to the accumulation of ICAM-1 containing circulating leukocytes in the lung. The role of ICAM-1 in the pathophysiology of oleic acid-induced lung injury and the mechanism by which oleic acid increases ICAM-1 expression in the lung therefore remain to be defined by future experimentation.

Intercellular adhesion molecule-1 (ICAM-1) expression in the islets of the non-obese diabetic and low-dose streptozocin-treated mouse.

The expression of intercellular adhesion molecule-1 (ICAM-1) was studied in 8-week-old non-obese diabetic (NOD) mice and low-dose streptozocin-treated (LDS) mice. ICAM-1 expression in NOD mice was observed at the islet periphery, corresponding to the peri-islet venular network, within the islet and on scattered elements along septa of the exocrine portion of the pancreas. Image analysis demonstrated that LDS-treated animals had less ICAM-1 immunoreactivity within and around the islets compared to NOD mice. At the ultrastructural level the peri-islet vessels were found to be filled with mononuclear elements. Moreover, endothelial cells showed signs of activation, and margination of monocytes and polymorphonuclear leukocytes was observed.

Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in undifferentiated nasopharyngeal carcinoma (lymphoepithelioma) and in malignant epithelial tumors

Immunoreactivity for intercellular adhesion molecule-1 (ICAM-1) and for vascular cell adhesion molecule-1 (VCAM-1), two adhesion molecules of the immunoglobulin (Ig) superfamily, was tested and measured on tissue sections from 16 undifferentiated nasopharyngeal carcinomas (U-NPC), 12 keratinizing squamous cell carcinomas (SCCs) of the head and neck region, and 54 malignant epithelial tumors of various origin. Neoplastic cells of all cases of U-NPC were diffusely and intensely stained for ICAM-1 and VCAM-1. Moreover, ICAM-1 messenger RNA (mRNA) and VCAM-1 mRNA were detected by Northern blot analysis of RNA extracts from two tumors. In the other epithelial tumors focal or diffuse staining for ICAM-1 was observed in 40 cases (66%), whereas reactivity for VCAM-1 was detected in a single case of metastatic undifferentiated carcinoma of unknown origin. The biopsy specimens of U-NPC showed variable infiltration by leukocytes, which were positive for the intergrins lymphocyte function antigen-1 (LFA-1) and alpha-4/beta-1, the corresponding ligands for ICAM-1 and VCAM-1. The possibility that ICAM-1 and VCAM-1 on neoplastic cells may favor the intratumoral recruitment of leukocytes in a way similar to that occurring in crypt epithelium of the palatine tonsil is discussed.

Expression of cell adhesion molecules in inflammatory myopathies and Duchenne dystrophy.

Cell adhesion molecules participate in target-effector cell interactions in cell-mediated cytotoxicity and in leukodiapedesis in inflammatory diseases. Two ligand-receptor pairs may play a role in the adhesion of cytotoxic T cells to their targets: 1) intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1), and 2) LFA-3 and CD2. We therefore immunolocalized these molecules in myopathies where there is evidence for T cell-mediated myocytotoxicity, namely inclusion body myositis, polymyositis, and Duchenne dystrophy. Autoaggressive inflammatory cells close to invaded muscle fibers showed an increased expression of ICAM-1 and LFA-1. The nonnecrotic muscle fibers invaded by autoaggressive cells expressed ICAM-1 where their surfaces faced the invading cells. That immunoreactivity for ICAM-1 on the invading cells was distinct from that on the opposite muscle fiber surface was established by colocalization of ICAM-1 with the sarcolemmal marker dystrophin (or beta-spectrin) and was also confirmed by confocal microscopy. Leukodiapedesis in inflamed tissues is mediated by ICAM-1, LFA-3, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin associated with endothelial cells. In dermatomyositis ICAM-1 was strongly expressed on endothelial cells of perimysial arterioles and venules and on some perifascicular capillaries. In all the other myopathies ICAM-1 and LFA-3 expressions were increased on endothelia of capillaries surrounded by inflammatory cells. VCAM-1 was detected in few arterioles in all diseases. E-selectin was not detected at any site in any disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of intercellular adhesion molecule-1 on cardiac myocytes for myocarditis before and during immunosuppressive therapy

Right ventricular endomyocardial biopsies were performed in 15 patients with unexplained cardiac dysfunction, and the expression of intercellular adhesion molecule-1(ICAM-1) on the myocardium was examined using the streptavidin-biotin complex method. Three of 15 patients (20%) had histologic evidence of myocardtis, and 2 of 15 patients (13%) had borderline myocarditis. The patients with biopsy-proven myocarditis received immunosuppressive therapy (prednisolone 60 mg/day). Two of the 3 patients demonstrated a substantial increase (>10%) in percent fractional shortening and left ventricular ejection fraction during therapy. Subsequent biopsies revealed ongoing myocarditis in 1 patient, and resolved myocarditis in the other. The remaining patient had persistent cardiac dysfunction, but the subsequent biopsy revealed resolving myocarditis. ICAM-1 immunoreactivity was observed on cardiac myocytes, vascular endothelial cells, and interstitial cells of the patients with myocarditis. However, in patients without myocarditis, ICAM-1 immunoreactivity was observed only on vascular endothelial cells and interstitial cells. ICAM-1 immunoreactivity was still observed on cardiac myocytes in the patients with ongoing or resolving myocarditis during immunosuppressive therapy, but was not detected in the patient with resolved myocarditis. This study demonstrates that ICAM-1 is expressed on cardiac myocytes of patients with myocarditis and persistent cardiac dysfunction despite immunosuppressive therapy. The persistent expression of ICAM-1 may cause chronic inflammation of the myocardium.

Expression of intercellular adhesion molecule-1 on rat microglial cells

Microglial cells isolated from newborn rat brain displayed a baseline immunoreactivity for intercellular adhesion molecule-1 (ICAM-1) after 10–20 days in culture. ICAM-1 immunoreactivity was enhanced in a time-dependent fashion by exposing the microglial cells to recombinant rat γ-interferon (γ-IFN; 100 U/ml) or tumor necrosis factor-α (TNF-α; 100 U/ml). We conclude that rat brain macrophages/microglial cells can be induced by γ-IFN and TNF-α to express ICAM-1. This may be relevant in the interaction of microglial cells with other brain cells during inflammation of the central nervous system.

Intercellular Adhesion Molecule-1 (ICAM-1) and HLA-DR Antigens in Herpes Keratitis

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface glycoprotein that binds leukocyte function antigen-1 receptor on leukocytes, thereby regulating leukocyte trafficking and function at sites of inflammation. Recently, the authors demonstrated ICAM-1 in human corneas exposed to proinflammatory cytokines, but ICAM-1 has not been reported in corneal disease. In this study, the presence of ICAM-1 in human disciform herpes simplex virus (HSV) keratitis is investigated. Immunohistochemistry was performed for ICAM-1 on 4 keratoplasty specimens from patients with corneal scarring due to disciform HSV keratitis and 1 corneoscleral biopsy of a patient with active HSV keratoscleritis using specific, characterized monoclonal antibody to ICAM-1. Negative immunohistochemical controls included monoclonal antibodies to other vascular endothelial adhesion molecules or mouse serum. All 5 specimens demonstrated intense ICAM-1 immunoreactivity of keratinocytes, stromal keratocytes, and endothelial cells, predominantly in regions of leukocytic infiltration. Diffuse, intense HLA-DR positivity was detected throughout the corneas. The specimens failed to react with control antibodies. These results are the first to demonstrate ICAM-1 in human corneal disease and suggest important roles for ICAM-1 and HLA-DR co-expression in generating immune responses in HSV keratitis. Increased ICAM-1 expression in regions of leukocytic infiltration may regulate leukocyte-corneal cell binding, thereby promoting immune responses and damage by activated leukocytes.

Cytokine-Induced Expression of Intercellular Adhesion Molecule-1 (ICAM-1) in Cultured Human Oligodendrocytes and Astrocytes

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) on primary cultures of human adult oligodendrocytes and astrocytes. Under unstimulated conditions, low levels of ICAM-1 immunoreactivity were identified on both oligodendrocytes (less than 50%) and astrocytes (less than 30%). After 48 hours' exposure to immune mediators, such as culture supernatant of phytohemagglutinin (PHA)-stimulated lymphocytes, interferon gamma (IFN-gamma; 1,000 U/ml), tumor necrosis factor alpha (TNF-alpha; 2,000 U/ml), interleukin-1 alpha (IL-1 alpha; 1,000 U/ml) and lipopolysaccharide (LPS; 50 micrograms/ml), ICAM-1 expression on both cell types was markedly increased in terms of intensity and cell numbers. IFN-gamma and culture supernatant of PHA-stimulated lymphocytes were the most potent inducers of ICAM-1 among the mediators tested, while TNF-alpha, IL-alpha and LPS were less effective, although variations were observed among cultures derived from different donors. Cytokine-induced expression of ICAM-1 on glial cells may play a role in mediating lymphocyte-glial cell interactions at sites of inflammation in the central nervous system.