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The functional importance of ICAM-1 and its ligands, the beta2-integrins, in leukocytic accumulation in pulmonary injury has been recently demonstrated in experimental models of lung disease. However, the exact location of these adhesion molecules remains unknown. In the current study we have used immunogold ultrastructural techniques to define the precise location of ICAM- 1 in the lung and its interaction with beta2-integrin expressing leukocytes in the early stages of experimental Goodpasture's (GP) syndrome in the rat. In normal animals there is strong constitutive ICAM-1 expression on the luminal surface of the alveolar epithelium that is confined to type I cells and completely absent from type II cells. Constitutive expression of ICAM-1 on the pulmonary capillary endothelium is comparatively weak. In GP syndrome there is an increase in ICAM-1 expression, which is still confined to the alveolar type I epithelial cells and capillary endothelium. This is associated with an early (1.5 hours) influx of CD18 expressing polymorphonuclear leukocytes, which are seen migrating into alveoli and the pulmonary interstitium. There is a later (6-12 hours) influx of CD11a/CD18 expressing macrophages which are present in the interstitium and in large numbers in the alveolar spaces, where they are very closely apposed to and adherent to the alveolar epithelium. This is the first study to demonstrate the precise ultrastructural location of ICAM-1 in the normal rat lung and in disease. In vivo administered antibody to ICAM-1 gains access to the extravascular sites within the lung, in particular the surface of alveolar type I epithelial cells, and this raises the possibility that beneficial effects of such antibodies may extend beyond their ability to inhibit interactions between leukocytes and endothelial cells.

The functional importance of ICAM-1 and its ligands, the beta2-integrins, in leukocytic accumulation in pulmonary injury has been recently demonstrated in experimental models of lung disease. However, the exact location of these adhesion molecules remains unknown. In the current study we have used immunogold ultrastructural techniques to define the precise location of ICAM- 1 in the lung and its interaction with beta2-integrin expressing leukocytes in the early stages of experimental Goodpasture's (GP) syndrome in the rat. In normal animals there is strong constitutive ICAM-1 expression on the luminal surface of the alveolar epithelium that is confined to type I cells and completely absent from type II cells. Constitutive expression of ICAM-1 on the pulmonary capillary endothelium is comparatively weak. In GP syndrome there is an increase in ICAM-1 expression, which is still confined to the alveolar type I epithelial cells and capillary endothelium. This is associated with an early (1.5 hours) influx of CD18 expressing polymorphonuclear leukocytes, which are seen migrating into alveoli and the pulmonary interstitium. There is a later (6-12 hours) influx of CD11a/CD18 expressing macrophages which are present in the interstitium and in large numbers in the alveolar spaces, where they are very closely apposed to and adherent to the alveolar epithelium. This is the first study to demonstrate the precise ultrastructural location of ICAM-1 in the normal rat lung and in disease. In vivo administered antibody to ICAM-1 gains access to the extravascular sites within the lung, in particular the surface of alveolar type I epithelial cells, and this raises the possibility that beneficial effects of such antibodies may extend beyond their ability to inhibit interactions between leukocytes and endothelial cells.

Objective - Emerging evidence suggests that human blood contains bone marrow (BM)-derived endothelial progenitor cells that contribute to postnatal neovascularization. Clinical trials demonstrated that administration of BM-cells can enhance neovascularization. Most studies, however, used crude cell populations. Identifying the role of different cell populations is important for developing improved cellular therapies. Methods and Results - Effects of the hematopoietic stem cell-containing CD34+ cell population on migration, proliferation, differentiation, stimulation of, and participation in capillary-like tubule formation were assessed in an in vitro 3-dimensional matrix model using human microvascular endothelial cells. During movement over the endothelial monolayer, CD34+ cells remained stuck at sites of capillary tube formation and time- and dose-dependently formed cell clusters. Immunohistochemistry confirmed homing and proliferation of CD34+ cells in and around capillary sprouts. CD34+ cells were transduced with the LNGFR marker gene to allow tracing. LNGFR gene-transduced CD34 + cells integrated in the tubular structures and stained positive for CD31 and UEA-1. CD34+ cells alone stimulated neovascularization by 17%. Coculture with CD34- cells led to 68% enhancement of neovascularization, whereas CD34- cells displayed a variable response by themselves. Cell-cell contact between CD34+ and CD34- cells facilitated endothelial differentiation of CD34+ cells. Conclusions - Our data suggest that administration of CD34+-enriched cell populations may significantly improve neovascularization and point at an important supportive role for (endogenous or exogenous) CD34- cells. © 2005 American Heart Association, Inc. Chemicals / CAS: nitric oxide, 10102-43-9; Antigens, CD34; Biological Markers

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