Submitted to: In Vitro Cellular And Developmental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/28/2002
Publication Date: 10/1/2002
Citation: KOENIG, J.M., BALLANTYNE, C.M., KUMAR, A.G., SMITH, W.C., YODER, M.C. VASCULAR CELL ADHESION MOLECULE-1 EXPRESSION AND HEMATOPOIETIC SUPPORTIVE CAPACITY OF IMMORTALIZED MURINE STROMAL CELL LINES DERIVED FROM FETAL LIVER AND ADULT BONE MARROW. IN VITRO CELLULAR AND DEVELOPMENTAL BIOLOGY. 2002. 38:538-543 Interpretive Summary: Liver can in a number of conditions function as a site for the production of blood cells (both red and white blood cells). While this is not the usual site for this production (normally it occurs in bone marrow), certain stimuli can induce conditions necessary for development of colonies of dividing cells from which normal mature blood cells arise. This activity appears depend on important tissue cells "stromal cells" that have special properties. In this paper we demonstrate the ability of the liver stromal cells to express on their surface an adhesion molecule (VCAM-1) that necessary for blood cell development.
Technical Abstract: Ontogeny-specific differences in hematopoietic behavior may be influenced by unique adhesive interactions between hematopoietic cells and the microenvironment, such as that mediated by vascular cell adhesion molecule-1 (VCAM-1, CD 106). Although VCAM-1 is variably expressed during vertebrate development, we hypothesized that VCAM-1 expression might be linked to the enhanced capacity of the fetal liver microenvironment to support hematopoiesis. To test this we used immortalized murine stromal cell lines derived from midgestation fetal liver and adult bone marrow to compare the functional expression of VCAM-1. Molecular analysis of VCAM-1 expression was performed on stromal cell lines using Northern blot analysis, immunoprecipitation studies, and solid-phase enzyme-linked immunosorbent assay. Hematopoietic studies were performed by coculturing fetal liver cells with stromal cell lines, and the functional readout was determined by high-proliferative potential colony-forming cell (HPP-CFC) adherence assays. In contrast to our initial hypothesis, we observed greater expression of VCAM-1 messenger ribonucleic acid and protein on an adult marrow stromal cell line. In functional studies, anti-VCAM-1 antibody inhibited the binding of nearly half of the HPP-CFCs to adult marrow stroma but had a minimal effect on their binding to fetal liver stroma, despite the greater adherence of HPP-CFCs to fetal stroma. We conclude that VCAM-1 influences the hematopoietic supportive capacity of immortalized murine stroma derived from adult bone marrow. Our studies suggest that cellular interactions other than those mediated by VCAM-1 are involved in the increased adhesive capacity of immortalized murine stroma derived from fetal liver.