The Nature of Ground Substance of Connective Tissue

THE NATURE OF GROUND SUBSTANCE OF CONNECTIVE TISSUE ISIDORE GERSH, Ph.D., and HUBERTR. CATCHPOLE, Ph.D.* In 1949 we proposed a relatively simple hypothesis concerning the nature of the ground substance of connective tissue. Since then we have continued working on this problem independently along different lines. One ofus (H. R. C.) with his colleagues has been working with electrometrical and chemical methods toward a better understanding of ground substance as a whole, considered as a physicochemical system. The other (I. G.) with his students has aimed at getting a closer view of the submicroscopic structure and relations ofground substance with the electron microscope. Now after ten years, our separate paths have converged. We feel that it may be profitable to attempt to integrate our newer findings with the earlier ones in order to develop, extend, and remodel the original hypothesis. The emphasis in this essay is placed on presenting a unified point of view, insofar as possible, which extends through our actual findings, interpretations , and speculations. Only enough data are given to clarify this point ofview, and the references to the original literature are accordingly limited. Many others could readily be cited, for and against the point of view we hold, and numerous other references could be collected in support ofother outlooks. In other words, this essay is designed to emphasize one particular way of looking at certain problems centering around the role ofthe ground substance ofconnective tissues; it is not intended as a summary ofthe literature in the field. Ten years ago we considered the ground substance ofconnective tissue to be the non-fibrillar, optically homogeneous, extra- (or inter-) cellular material (1). This was stainable under certain conditions in sections with the periodic acid leukofuchsin stain (PAS) or metachromatically with * Department ofAnatomy, University ofChicago, and Department ofPathology, University of Illinois, Chicago, Illinois, respectively. The original work referred to in this essay was supported by the Commonwealth Fund, the Clara A. and Wallace C. Abbott Research Fund ofthe University of Chicago, U.S.P.H.S. Grant A-968-C3, and the Graduate School, University ofIllinois. 282 Isidore Gersh and Hubert R. Catchpole · Connective Tissue Ground Substance Perspectives in Biology and Medicine · Winter i960 toluidine blue or intravitally with Evans blue. In certain sites (adjacent to epithelia and around muscle fibers, fat cells, and capillaries) the ground substance stained more deeply than the normal ground substance with which it was continuous, and we referred to this sheet ofenhanced stainabilityasthehomogeneous component ofbasement membranes (seeFig. ?). The most important property ofground substance studied was the solubility of its stainable components in water. The solubility differs in the various organs and, more importantly, in different functional states of several organs as well as at different ages in the same organ. This was the main basis for the hypothesis that ground substance may be organized as a polymer. It was thought to be highly polymerized when it was insoluble in water and depolymerized when soluble. Intermediate degrees of polymerization were indicated by the depth of staining with the PAS EPITHELIUM ELASTIC FIBER COLLAGEN FIBER FAT CELL CAPILLARY WITH RED BLOOD CELL MUSCLE FIBER Rg. i.—Diagram ofrelations of connective tissue ground substance (stippled) to cells and fibers. More heavily stippled regions adjacent to certain cells are the homogeneous component of the basement membrane. In addition to labeled cells, additional cells are represented: fibroblast, mast cell, macrophage, small wandering cell. 283 method. We suggested that, when ground substance components became soluble, they could pass into the circulating blood and raise the level of plasma mucoproteins. The ground substance was regarded as being primarily oflocal origin (arising as a secretion from fibroblasts) and coextensive with the tissue fluid derived from the plasma.1 I. Definition of "Ground Substaitce" The term "ground substance" seems to be unacceptable to numerous workers because the word "substance" implies that its chemical composition is known and that one such chemical is involved. This is clearly a matter ofsemantics. Ground substance includes a large, and to a great extent unknown, variety of chemical substances, some of which probably arise locally, some from the plasma, and some from both sources. The major components of ground substance may be tabulated (Table i). In...