血管细胞粘附分子调控造血的研究进展

本文简述了血管细胞粘附分子 (Vascularcelladhesionmolecule 1,VCAM 1)的结构和生物学功能 ,总结了VCAM 1在恶性血液病骨髓基质中的表达和意义 ,探讨了VCAM 1在造血干细胞动员和归巢中的作用 ,指出VCAM 1作用机制的深入研究将对恶性血液病的治疗提供更为有效的方法。     

Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa

Previous studies have suggested that human follicular fluid contains factors that reduce the zona-binding capacity of spermatozoa. The present study provides further evidence of the existence of such factors. Using the hemizona binding assay (HZA), we have shown that the inhibitory effect of human follicular fluid on the zona-binding capacity of spermatozoa is concentration-dependent, an inhibitory effect being detected when the concentration of human follicular fluid was > or = 10%. A 1% concentration of human follicular fluid did not possess this inhibitory activity. Heating human follicular fluid at 56 degrees C for 30 min did not affect its inhibitory properties; treatment with proteinase-K abolished such inhibition. Human follicular fluid was fractionated sequentially by concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography and Superose-12 gel filtration. The zona binding inhibitory activity resided in the fraction which bound to the lectin and Mono Q column and contained molecules with native molecular weights of 32 and 192 kDa. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein remained as a single molecular species under denaturing conditions. We conclude that two glycoproteins were responsible for the zona binding inhibitory activity of human follicular fluid. The physiological role of these factors remains unclear.      

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165     

Modulation of in vitro eosinophil progenitors by hydrocortisone: role of accessory cells and interleukins

The growth of human eosinophil progenitors (CFU-Eo) and the modulation of growth by hydrocortisone were studied as functions of the presence of lymphocytes and monocytes in marrow cells under study; and the source of colony-stimulating factors, specifically, media conditioned by macrophage-like cell line, GCT; phytohemagglutinin-stimulated mononuclear cells (PHA-LCM); or the T cell line, MO. CFU-Eo growth was greatest in marrow containing accessory cells as compared to marrow depleted of accessory cells; and in marrow treated with phytohemagglutinin-stimulated leukocyte conditioned media (PHA-LCM) or MO (T cell line)-conditioned medium (MO-CM) as compared with GCT cell- conditioned medium (GCT-CM). Hydrocortisone reproducibly inhibited eosinophil progenitor growth in unfractionated marrow stimulated by GCT- CM. This effect was abrogated by admixing irradiated mononuclear cells or T lymphocytes with the target marrow or by adding interleukin 1 or interleukin 2 (IL-1, IL-2). Inhibition by hydrocortisone did not occur when monocyte and T lymphocyte depleted marrow was studied. Unlike GCT- CM, MO-CM and PHA-LCM stimulated equal proportions of eosinophil progenitors in nondepleted and accessory cell-depleted marrow and demonstrated less hydrocortisone inhibition. However, both GCT-CM and PHA-LCM produced in the presence of hydrocortisone stimulated significantly fewer CFU-Eos in both unfractionated and accessory cell- depleted marrow target populations. These results indicate that the growth of CFU-Eo and inhibition of growth by hydrocortisone is a direct function of a monocyte-T cell interaction and probably is mediated through effects on the production/release of eosinophil colony stimulating factor (Eo-CSF).     

Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium

Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.     

Passive smoking increases platelet thromboxane

Although active smoking is known to enhance platelet thromboxane production, no data on passive smoking are available yet. In an 18 m³ room, the influence of single and repeated exposure to passive smoke for 60 minutes was assessed in nonsmokers and smokers. Smokers and nonsmokers were matched for sex and age. All the evaluated parameters (plasma TXB₂, serum TXB₂, malondialdehyde, 11-dehydro-TXB₂, conversion of exogenous arachidonic acid to hydroxy-5,8,10-heptadecatrienoic acid, and TXB₂) were higher in smokers than nonsmokers at baseline conditions, immediately and 6 hours after passive exposure to cigarette smoke. Repeated exposure of nonsmokers rendered their platelets more activated, so they became closer to the behavior of smokers. Contributing to the development of hemostatic imbalance, these results indicate that passive smoking may enhance thromboxane A₂ release from the platelets.Presented at the 36^th Annual World Congress, International College of Angiology, New York, New York, July 1994