To evaluate immunologic function of vascular endothelial cells, we have set up an immunohistochemical study on the adhesion molecules in inflammatory bowel disease (IBD). ln IBD, vascular endothelial cells became morphologically active; ie., they became swollen and had well developed cell organelles. Intercellular adhesion molecule-1 (ICAM-1) was expressed in plasma cells, lymphocytes, macrophages and vascular endothelial cells. Its counter-receptor, lymphocyte function associated antigen (LFA-1) was localized in lymphocytes. The expression of these molecules increased remarkably in IBD than in the normal intestinal or colonic mucosa. MHC class II antigen was also expressed abundantly in IBD. Vascular endothelial cells of venules expressed endothelial leukocyte adhesion molecule-1 (SLAM-1) in active inflammatory phase. Its expression was sporadic in the resolving phase of inflammation and the normal mucosa. Our study suggests that vascular endothelial cells regulate the permeation of inflammatory cells into the tissue from the blood by expressing the adhesion molecules. The common expression of ICAM-1 and HLA-DR antigens with macrophages indicates the presence of a unit of endothelial cells and macrophages in eliciting and/or maintaining the inflammation.

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We investigated the immunohistochemical characters about structure and ontogenic development of sheath artery and ellipsoid of White Leghorn chicken spleen. We succeeded to establish two newly monoclonal antibodies, named CSA-1 and CSA-2. CSA-1 reacted not only with all vascular endothelial cells, but also with fibroblastic reticulum cells of the inner zone of ellipsoid. CSA-2 detected dendritic cells surrounding the outer zone of ellipsoid, on which class II major histocompatibility complex (MHC) were expressed. In the ontogenic study, it was shown that CSA-1-positive reticulum cells appeared on day 18th of fetal stage, which was the critical date when the tight junction of endothelial cells of sheath artery disappeared. And CSA-2-positive dendritic cells and macrophages accumulated around sheath artery on the same day 18th. Using anti-chicken class II MHC monoclonal antibody, CBL-1, macrophages and dendritic cells of ellipsoid were possitive, but endothelial cells of sheath artery were negative against CBL-1. Even with immunological activation by intravenous injection of horseradish peroxidase, endothelial cells didn't express class II MHC. Therefore, it is strongly suggested that macrophages and dendritic cells of ellipsoid, but endothelial cells, play important roles in immune response.

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To clarify the pathobiology of the Fc receptors in the liver sinusoidal endothelium, the Fc receptors were studied by applying peroxidase-antiperoxidase IgG complexes as a ligand to frozen tissue sections from human cirrhotic livers, rat cirrhotic livers induced with CC14, rat regenerating livers after 70 per cent hepatectomy, livers of NZB/WF1 mice and livers of the mice injected intracutaneously with complete Freund's adjuvant (CFA). The Fc receptors showed a focal absence and the length of the Fc receptor-positive portions of the sinusoids in unit area decleased to about 50% and 60% of the normal value in the advanced cirrhosis in man and rats, respectively. The delayed blood clearance and decreased hepatic uptake of ¹²⁵I-labeled BSA-antiBSA IgG comlexes were seen in the cirrhotic rats. The Fc receptor activity, estimated by staining intensity of the Fc receptors, was considerably decreased is the regenerating livers for 7 days after hepatectomy. The 5-week-to 9-month-old NZB/WF1 mice showed higher Fc receptor activity than control NZW mice. The Fc receptor activity in the CFA injected mice gradually increased until 4 week after administration. The hyperplasia or absence of Kupffer cell was found in these conditions, associated with increase and decrease of Fc receptor activity, but the causative relationship between Kupffer cell number and Fc receptor activity could not be found.

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In order to clarify the role of macrophages and endothelial cells in low density lipoprotein (LDL) metabolism, we have performed the immunohistochemical and immunoelectron microscopic studies of tissue distribution, intracellular localization, and expression of scavenger receptors and LDL receptors.
Scavenger receptors are a trimeric membrane protein mediating endocytosis of modified LDL including acetylated LDL (acLDL). The receptors were detected specifically in macrophages in various tissues. Reaction products for scavenger receptors were localized on the cell surface, vesicles, and endosomes.
As for the intracellular localization of scavenger receptors during receptor-mediated endocytosis of acLDL, we demonstrated that the receptors were internalized through coated pits and moved into endosomes and recycled to the cell surface via Golgi apparatus. Expression of scavenger receptors in cultured macrophagic and non-macrophage cells suggested that efficient intracellular transport of the receptors is mediated by a macrophage specific transport system.
Endothelial cells have LDL receptors but not scavenger receptors. However, they bound to and took up both LDL and acLDL into the cytoplasm. These results suggest that endothelial cells possess different receptors capable of scavenging acLDL. Endothelial cells were considered to share intermediate characteristics between fibroblasts and macrophages in LDL metabolism.

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Influence of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL-1β) on the expression of thrombomodulin (TM, anticoagulant factor) and tissue factor-like procoagulant activity (PA, procoagulant factor) on cultured human umbilical vein endothelial cells and the effect of retinoic acid (RA, vitamin A acid) on the behavior of TM and PA in the cells caused by the cytokines were investigated. TNF-α and IL-1β induced the reduction of TM expression and elevation of PA in the cells in a dose-dependent manner in a range between 1 and 100U/ml. The reduction of TM expression by the cytokines accompanied with the decrease in TM mRNA levels, and the elevation of PA was inhibited by treatment with cycloheximide, inhibitor for protein synthesis. The current results indicate that the cytokines markedly increase procoagulant properties on the cell membrance through both the reduction of anticoagulant factor and the elevation of procoagulant factor, and suggest that the behaviors of anti- and pro-coagulant factor caused by the cytokines results from changes in protein synthesis. Treatment of the cells with RA prevented both the reduction of TM expression and the elevation of PA on the cell membrane caused by TNF-α treatment, in a dose-dependent manner in a range between 0.01 and 10μM. RA increased TM mRNA levels in the cells. It was suggested that RA regulates the balance between the expression of anti- and pro-coagulant factors on the cell membrance through regulation of gene transcription levels.

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Interrelation between mononuclear phagocyte system (MPS) activation and hemostatic abnormality was investigated in 3 patients with hemophagocytic histiocytic syndrome (HH), a representative clinical model of MPS proliferative disorders, accompanied by disseminated intravascular coagulation syndrome (DIC) and multiple organ failure (MOF). A markedly significant decrease of plasma free protein S (PS) levels was found with markedly raised plasma C4b-binding protein (C4bp) levels as compared to non-HH DIC patients with MOF. And also an extreme increase of plasma plasminogen activator inhibitor 1 (PAI-1) and von Willebrand factor antigen (vWF: Ag) levels was found. Moreover, a significant elevation of serum cytokines, especially interleukin-1β and tumor necrosis factor α, was observed when compared to non-HH DIC patients with MOF. Plasma free PS was inversely correlated with these cytokines, while each of C4bp, PAI-1 and vWF: Ag was positively correlated with them.
These results imply that markedly reduced plasma free PS and extremely increased plasma PAT-1 and vWF: Ag, which were possibly caused by the modulation of liver cells or vascular endothelial cells by these increased cytokines, would contribute to the pathogenesis of hemostatic abnormalities, particularly DIC and/or MOF in HH.

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Five cases of the pulmonary non-Hodgkin's lymphoma, B cell type were examined for clinicopathological, immunohistochemical and electron microscopical studies. We divided them into two groups. The first group had no symptomes and good prognosis. They were diagnosed as non-Hodgkin's lymphoma, diffuse, small cell or medium sized cell type. They histologically showed the typical “lymphoepithelial lesion” and less destructive infiltration with unclear margin of the tumor. The second group had pulmonary symtomes and poor prognosis with histology of non-Hodgkin's lymphoma, diffuse, large cell type. They showed destructive infiltration with relatively clear margin of the tumor and no lymphoepithelial lesion. There was some immunohistochemical difference between both groups. The former corresponded with MALT (muocsa-associated lymphoid tissue) lymphoma. The latter was an aggressive lymphoma and had much in common with features of nodal lymphomas. We concluded that a group of MALT lymphoma gave some characteristics of the pulmonary non-Hodgkin's lymphoma.

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Lymphocyte function-associated antigen-1 (LFA-1), a heterodimer glycoprotein consisting of α and β chains, belongs to a integrin superfamily and is known to distribute widely on lymphohemopoietic cells. In this study, we investigated LFA-1 expression in 52 cases of non-Hodgkin's lymphoma and 32 cases of reactive lymphoproliferative disease using an immunohistochemical method. The proportion of LFA-1 positive cells among mononuclear cells in all specimens was scored as follows: grade 0 (0∼10%), grade 1 (10∼50%), grade 2 (50∼80%). and grade 3 (80∼100%). In reactive lymphoproliferative diseases, none of the cases belonged to the category of grade 0 or 1, and more than 80% were classified as grade 3. In contrast, more than 50% of non-Hodgkin's lymphomas were scored as grade 0 or 1. Therefore monoclonal antibodies to LFA-1 may be the useful antibodies for the evaluation of malignancy in lymphoproliferative diseases. We found no correlation between histological classification and LFA-1 expression of B cell lymphomas, and there was a tendency that T cell lymphomas were classified in higher grade than B cell lymphomas. In some cases, we analysed LFA-1 expression by flow cytometry. By this method, a small number of LFA-1 negative lymphoma cells among many LFA-1 positive normal lymphocytes could be exactly identified.
So, flow cytometric analysis is necessary for the exact and objective evaluation of LFA-1 expression.

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A 37-year-old man with hemophilia A and an asymptomatic carrier of HIV infection developed convulsion in January 1989. Except for seborrhoic eczema on his face and head, the results of the physical examination were unremarkable. The white cell count was 2.3×10³/μl with 14% lymphocytes. His CD4/CD8 ratio was 0.27 with 11.5% CD4 cells and 43.0% CD8 cells. Absolute numbers of CD4⁺- lymphocytes were 37/μl. A ring-shaped enhancing lesion with surrounding edema was disclosed in the right frontal region by computed tomographic scan. Cranial irradiation resulted in an increase of the mass and the development of left hemiparesis. Four pieces of cerebral tissue obtained by biopsy revealed necrosis with degeneration. Thereafter, he had a rapidly declining course, characterized by coma and pneumonia, and died in April 1989. Autopsy revealed cerebral toxoplasmosis, bronchopneumonia without pneumocystis carinii pneumonia, marked atrophy of systemic lymphnodes, and chronic hepatitis.

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We report an autopsy case of angiocentric lymphoma initially manifested as lymph node infarction. The second biopsy obtained from the other lymph node showed a diffuse proliferation of various-sized lymphoid cells with cytologic atypia. Cellular infiltration to vascular walls accompanied by irregular necrotic areas was observed. Immunohistological study of the lymph node expressed the phenotype (CD3⁺CD8⁺CD4^±), consistent with that of peripheral T-cell lymphoma, except that some large lymphoid cells were positive for B-cll specific antibody L26.
The autopsy showed extensive lymphoma cell infiltration of the liver, spleen, kidneys, lungs, gastrointestinal tract, nasopharynx, and lymph nodes. Of interest, the angiocentric and angioinvasive nature of the lymphoma cell infiltration was evident, and necrosis of tissues was accompanied by the infiltration. These features are characteristic of angiocentric lymphoma, and retrospective studies suggest that the lymph node infarction was caused by angiocentric immunoproliferative lesions introduced by Jaffe in 1984.
Southern blot analysis of DNA extracted from the lymph nodes of the second biopsy and of the autopsy showed germline configurations for T-cell receptor (TcR) β-chain, δ-chain and immunoglobulin heavy chain genes. Only TcR γ-chain exhibited multiple faint rearrangement bands, but this is compatible with polyclonal T-cell proliferation. The results obtained through our studies, in addition to the previously reported cases, suggest that certain types of peripheral T-cell lymphoma may lack clonal rearrangements of TcR genes.

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