Blood platelets stimulate the expression of chondroitin sulfate proteoglycan in human monocytes

Abstract

Mononuclear phagocytes synthesize chondroitin sulfate proteoglycan (CSPG), which is constitutively secreted. Because mononuclear phagocytes are known to interact with blood platelets, the effect of platelets on the release of CSPG in cultured human monocytes was investigated. After 6 days in vitro, the monocytes were supplied with fresh medium with different additions and subsequently exposed to [35S]sulfate for 24 hours before the medium fractions were harvested and analyzed for content of [35S]CSPG. Indirect evidence for the release of stimulatory factors from blood platelets was found when the addition of medium containing 50% serum made from platelet-rich plasma increased the expression of [35S]CSPG almost sevenfold compared with serum-free medium, whereas medium containing 50% serum made from platelet-depleted plasma increased the expression of [35S]CSPG about fourfold. Further, direct evidence for the stimulatory effect of platelets was found as the addition of autologous platelets to serum- free medium increased the expression of [35S]CSPG about threefold, and addition of supernatant from a corresponding number of thrombin- stimulated platelets was almost as efficient. The effect of five different platelet-derived factors (which are all present in serum) was investigated. Both platelet-derived growth factor (PDGF), platelet factor 4 (PF 4), and prostaglandin E2 (PGE2) used in physiologic concentrations were found to stimulate the expression of [35S]CSPG twofold to threefold, whereas transforming growth factor-beta had a slight inhibitory effect. 12-Hydroxyeicosatetraenoic acid had no significant effect on the expression of [35S]CSPG. Further evidence for the stimulatory effect of PDGF, PF 4, and PGE2 was found as serum depleted of these factors had significantly less stimulatory effect than control serum. The increased incorporation of [35S]sulfate into [35S]CSPG in cultures stimulated with serum or platelet-derived factors was not due to differences in molecular size or extent of sulfation of the proteoglycan molecules.

Chondroitin Sulfate Proteoglycans and Microglia Prevent Migration and Integration of Grafted Müller Stem Cells into Degenerating Retina

“…We observed, in accordance with other studies, that the retina of the dystrophic RCS rat shows heavy accumulation of the N terminus of chondroitin sulfate proteoglycans [37], neurocan [38], and versican. Our results further demonstrated that microglia, which are known to produce CSPGs in vitro [39] and in vivo upon spinal cord injury [40,41], also express the N-terminal fraction of CSPGs, as well as neurocan and versican in the degenerating RCS rat retina. Significantly, costaining of retinal sections from transplanted RCS rat retinae for CSPGs and CD68 expression showed that microglia surrounding the grafted cells stained for CSPGs.…”

Modifications in the synthesis of membrane‐associated chondroitin sulfate proteoglycans in hemopoietic progenitor cells are accompanied by alterations in their adhesive properties

“…Besides this effect, chlorate prevents scavenging of sulfate from cysteine (Krijgsheld et al, 1981) and reduces sulfate incorporation into PG, without affecting protein synthesis, phosphorylation, and cell morphology (Baeurle and Huttner, 1986;Rapraeger et al, 1991). On the other hand, p-xyloside derivatives at concentrations s 1 mM compete with endogenous xylosilated core proteins for GAG synthesis in a mode that is virtually confined to species containing chondroitid dennatan sulfate chains (Schwartz, 1977;Uhlin-Hansen and Kolset, 1988;Rapraeger, 1989;Kirby and Bentley, 1991).…”

“…This feature of hemopoietic cells is intriguing, because cells other than hemopoietic synthesize diverse types of proteoglycans (Poole, 1986). Intracellular serine-glycine-rich chondroitin sulfate proteoglycans (CS-PG) are generally stored as secretory granules by diverse types of hemopoietic cells (Hardin and Spicer, 1971;Uhlin-Hansen and Kolset, 1988;Krilis et al, 1992). The function of these components has not been fully elucidated.…”

Serglycin secreted by leukocytes is efficiently eliminated from the circulation by sinusoidal scavenger endothelial cells in the liver

“…In addition, serglycin seems to be important in the regulation of the activity of the bound enzymes [9,10]. In contrast to the granular cells that store serglycin in the secretory granules, monocytes and lymphocytes secrete serglycin constitutively [11][12][13]. The secreted serglycin might serve as a carrier of other molecules, e.g., proteases and cytokines released from the cells.…”