Connective tissue activation. XIV. Composition and actions of a human platelet autacoid mediator.
Connective tissue activation. XIV. Composition and actions of a human platelet autacoid mediator.
复制标题
结缔组织激活。
作者：
Castor Cw;Ritchie Jc;Williams Ch;Scott Me;Whitney Sl;Myers Sl;Sloan Tb;B. Anderson
从人血小板中分离得到的结缔组织激活肽-III(CTAP-III)除了刺激糖胺多糖合成、葡萄糖消耗和乳酸形成外，还是一种有效的促结缔组织细胞有丝分裂的物质。测定了表面均一的CTAP-III的氨基酸组成，证实了两个二硫键的存在，并提供了计算的相对分子质量为11,633道尔顿。血清和血浆的促有丝分裂活性比较表明，CTAP-III是人血清的主要促有丝分裂成分。17株人结缔组织细胞(滑膜、软骨、真皮和甲状腺)在微克量CTAP-III的影响下，掺入[~3H]-胸腺嘧啶核苷的水平可达对照的30倍，并可使低至10-29 ng/ml的胸腺嘧啶核苷掺入量显著增加，前列腺素E_1(0.01微克/毫升)和二丁酰环腺苷(25微克/毫升)可增强CTAP-III的糖胺多聚糖刺激作用，但不能促进其促分裂作用。放线菌素D和放线菌素D阻断了CTAP-III的生物学作用。皮质醇和青霉胺对CTAP-III的促有丝分裂活性影响不大，而抗风湿剂如乙酰水杨酸和苯丁酮在加入临床相关浓度的培养物中时，对有丝分裂活性有抑制作用。低亲和力血小板因子4(LA-PF4)是一种由血小板分泌的弱抗肝素因子，在生物学作用、凝胶迁移率、氨基酸组成和抗原决定簇等方面与CTAP-III相似。
Connective tissue activating peptide-III (CTAP-III) isolated from human platelets is a potent mitogen for human connective tissue cells in culture in addition to stimulating glycosaminoglycan synthesis, glucose consumption, and lactate formation. The amino acid composition of apparently homogeneous CTAP-III was determined, confirming the presence of two disulfide links and providing a calculated molecular weight of 11,633 daltons. Comparison of the mitogenic activity of serum and plasma-serum suggests that CTAP-III is a major mitogenic component of human serum. Seventeen strains of human connective tissue cells (synovial, cartilage, dermal and thyroid) incorporated [3H]-thymidine at up to 30 times control at levels under the influence of microgram quantities of CTAP-III and caused detectable increases in thymidine incorporation at levels as low as 10-29 ng/ml. Prostaglandin E1 (0.01 microgram/ml) and dibutyryl cyclic AMP (25 microgram/ml) potentiated the glycosaminoglycan stimulating effect of CTAP-III, but not its mitogenic effect. Cycloheximide and actinomycin D blocked the biologic actions of CTAP-III. Cortisol and penicillamine had little effect on the mitogenic activity of CTAP-III, whereas antirheumatic agents such as acetylsalicylic acid and phenylbutazone opposed the mitogenic activity when added to cultures at clinically relevant concentrations. A weak antiheparin factor secreted by platelets, low affinity platelet factor 4 (LA-PF4), was shown to be similar to CTAP-III in biologic actions, electrophoretic mobility, amino acid composition, and antigenic determinants.