We continue our studies into structure-function relation in hemopoiesis. Our main focus is on the marrow sinus wall and the function of endothelium in controlling the selective transport of cells and molecules between the lumen and hemopoietic compartment (the marrow-blood barrier).
Our specific aims are: (1) To gain insight into the nature of selectivity of this transport, we shall map various lectin receptor sites and lectin-like substances on the endothelial surface using transmission (TEM) and scanning (SEM) electron microscopy. Lectin-binding sugars and lectin-like substances have now strongly been implicated as mediators of recognition. Latex minibead-or ferritin-conjugated lectins and glycosylated ferritins will be used as probes. These maps will be correlated with the sites of transport of cells and molecules. (2) We shall use serval tracer particles to systematically study the permeability of endothelium to substances of various size using TEM and freeze-fracture (FF) technique. We shall characterize the routes of transport and correlate them to particle size. (3) To determine if receptor-mediated mechanisms mediate transvascular traffic of some molecules, we shall search for the presence of transferrin and transcobalamin receptors on the endothelial surface. This is done by conjugating these proteins to either ferritin or latex minibeads and using SEM and TEM. (4) In some of these studies we shall compare normal marrow with marrow in which cellular traffic is experimentally altered (phlebotomy, transfusion plethora, Shay chloroleukemia). We shall then search for structural-functional correlates. (5) We shall study the development of marrow stroma and sinuses in ectopic marrow implant. In this model the ontogeny of marrow is recapitulated and marrow stroma is reconstituted before hemopoiesis is resumed. The model permits studying the marrow development in a relatively short time. We shall study the structure of stroma before and during the initiation of hemopoiesis in order to draw structural-functional correlate. We shall study the structure of developing sinuses by the methods described in this model, before and during the initiation of hemopoiesis and compare our findings with adult marrow. (6) We shall attempt to develop methods that may permit such studies in human marrow biopsy specimen. Through these studies we hope to learn somethin about the function of marrow and hence the pathogensis of marrow disease.
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