Hematopoiesis is, in part, regulated by direct cell-to-cell contact between developing blood cells and non-hematopoietic stromal cells. Stromal cells, through their elaboration of an extracellular milieu, promote cellular recognition, adhesion, and proliferation of a given line of blood cells. The nature of the extracellular components and their roles in hematopoiesis are largely unknown. Therefore, the proposed study will combine ultrastructural, histochemical, and biochemical work to study extracellular components shown to have regulatory functions in other developing systems. Glycosaminoglycans and sialic acid will be identified and quantitated in hematopoietic regions using quantitative histochemical and biochemical studies. Intracellular junctions will be located and their nature determined in freeze-fracture studies. The developmental regulation of lectins will be determined through histochemical, immunocytochemical, and biochemical analysis. Chick embryos will be used for all of these studies because the segregation of their marrow into topologically distinct erythropoietic and granulopoietic compartments will facilitate differential analysis of the role of extracellular components. Specific strains of avian leukemia viruses are available to make either erythropoietic or granulopoietic compartments hyperplastic. These studies will therefore increase our understanding of how basic developmental events operate in hematopoiesis and how blood-stromal cell interactions are affected by leukemic transformations. Avian hematopoiesis is sufficiently similar to its mammalian counterpart that the information derived from these studies can be applied to furthering our knowledge of how human hematopoiesis operates in normal and leukemic states.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
West Virginia University
School of Medicine & Dentistry
United States
Zip Code
Sorrell, J M; Caterson, B; Caplan, A I et al. (1990) Human keratinocytes contain carbohydrates that are recognized by keratan sulfate-specific monoclonal antibodies. J Invest Dermatol 95:347-52
Sorrell, J M; Caterson, B (1990) Monoclonal antibodies specific for keratan sulfate detect epithelial-associated carbohydrates. Histochemistry 94:269-75
Sorrell, J M; Mahmoodian, F; Schafer, I A et al. (1990) Identification of monoclonal antibodies that recognize novel epitopes in native chondroitin/dermatan sulfate glycosaminoglycan chains: their use in mapping functionally distinct domains of human skin. J Histochem Cytochem 38:393-402
Adany, R; Heimer, R; Caterson, B et al. (1990) Altered expression of chondroitin sulfate proteoglycan in the stroma of human colon carcinoma. Hypomethylation of PG-40 gene correlates with increased PG-40 content and mRNA levels. J Biol Chem 265:11389-96
Sorrell, J M; Caterson, B (1989) Detection of age-related changes in the distributions of keratan sulfates and chondroitin sulfates in developing chick limbs: an immunocytochemical study. Development 106:657-63
Sorrell, J M (1988) Ultrastructural localization of fibronectin in bone marrow of the embryonic chick and its relationship to granulopoiesis. Cell Tissue Res 252:565-71
Sorrell, J M; Lintala, A M; Mahmoodian, F et al. (1988) Epitope-specific changes in chondroitin sulfate/dermatan sulfate proteoglycans as markers in the lymphopoietic and granulopoietic compartments of developing bursae of Fabricius. J Immunol 140:4263-70
Sorrell, J M (1988) Development of arteries in embryonic chick bone marrow with special reference to the appearance of periarterial granulopoietic sheaths. Anat Rec 221:730-6
Sorrell, J M; Mahmoodian, F; Caterson, B (1988) Immunochemical characterization and ultrastructural localization of chondroitin sulfates and keratan sulfate in embryonic chick bone marrow. Cell Tissue Res 252:523-31
Sorrell, J M (1988) Ultrastructural localization of peanut lectin binding to extravascular white blood cells in the bone marrow of embryonic chicks. Cell Tissue Res 251:301-5

Showing the most recent 10 out of 11 publications