Heparin interaction with cultured cells: possible role of fibronectin in uncoupling surface binding and endocytosis.
Cellular uptake of 3H-heparin by cultured Chinese hamster ovary cells does not follow the pattern that would be expected on the basis of binding kinetics. It is essentially non-saturable and its low pinocytotic index is consistent with fluid-phase endocytosis, while surface binding is saturable and suggests the presence of specific receptors. Most of the surface-bound heparin is released into the medium and only minimal amounts are internalized when temperature is shifted from 0 degree to 37 degrees C. This uncoupling of surface binding and endocytosis may be due to the binding of heparin to an external surface macromolecule that is only loosely attached to the plasma membrane, and may therefore escape endocytosis. Fibronectin is a likely candidate to provide that type of binding site. Heparin has been found to bind specifically to a number of mammalian cells (Kjellen et al., 1977; Glimelius et al., 1978; Shanberge et al., 1976; Fabian et al., 1978), but no attempt was made in those studies to distinguish between surface binding and cellular uptake. Heparin is transported into cells when complexed to other macromolecules (Fabian et al., 1978; Shen and Ryser, 1981; Morad et al., 1982) and does then exert some cellular effects (Shen and Ryser, 1981). Despite the wide clinical use of heparin, little is known about its membrane transport and intracellular effects, although endocytosis of other polyanions has been shown to inhibit phago-lysosomal fusion in macrophages (Geisow et al., 1980).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis; D005260:Female; D005353:Fibronectins / Q000494:pharmacology / Q000502:physiology*; D006493:Heparin / Q000378:metabolism*; D007700:Kinetics; D010053:Ovary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013696:Temperature
D005353:Fibronectins; D011956:Receptors, Cell Surface; C037680:heparin receptor; D006493:Heparin