Lando P A, Edgington T S
Infect Immun. 1985 Dec;50(3):660-6. doi: 10.1128/iai.50.3.660-666.1985.
A number of species respond to bacterial endotoxin (lipopolysaccharide [LPS]) wherein cells of the monocyte-macrophage lineage are rapidly induced either directly or via T-cell collaboration to initiate the extrinsic coagulation protease pathway. This results in fibrin formation and deposition as well as consumption of plasma coagulation proteins. It has been claimed that this cellular response, basic to the Shwartzman reaction, is lacking in rats and may account for the more limited severity of the Shwartzman reaction in this species. We examined the in vitro lymphoid procoagulant response in Fischer 344, Brown Norway, and Lewis rats. When peripheral blood mononuclear cells (PBM) were stimulated in vitro with LPS, a procoagulant activity (PCA) response was observed when assayed by acceleration of clotting of recalcified human or rat platelet-poor plasma. The response was rapid, with a maximum achieved at 4 h. PCA was not physically dissociated from viable PBM by 5 mM EDTA, which is consistent with the presence of an intrinsic plasma membrane initiator molecule rather than calcium-bound gamma-carboxylated glutamic acid-containing proteases. The induction of monocyte PCA was prevented by incubation of cells with cycloheximide or actinomycin D, implicating a new biosynthetic requirement. Cultivation of PBM with warfarin did not diminish the function of the effector PCA, nor did vitamin K augment the function of the endotoxin-induced PCA, indicating that the functional activity was not attributable to gamma-carboxylated glutamic acid-containing proteins. No inhibition of the cellular PCA molecule was produced by serine protease inhibitors. The LPS-induced PCA appeared to involve a tissue factor-like molecule since both factors X and VII were required in mediating PCA. Isolation of monocytes and T lymphocytes from LPS-stimulated PBM demonstrated that PCA was present in the monocyte-rich fraction. When isolated rat T lymphocytes and monocytes were separately exposed to LPS, PCA was not induced. In contrast, when the cells were combined, LPS induced PCA, indicating that the PCA response involved cellular collaboration between cells present in T lymphocyte and monocyte populations.
许多物种会对细菌内毒素（脂多糖[LPS]）产生反应，其中单核细胞 - 巨噬细胞谱系的细胞会被直接或通过T细胞协作迅速诱导，从而启动外源性凝血蛋白酶途径。这会导致纤维蛋白的形成和沉积，以及血浆凝血蛋白的消耗。据称，这种对施瓦茨曼反应至关重要的细胞反应在大鼠中不存在，这可能是该物种施瓦茨曼反应严重程度较为有限的原因。我们检测了Fischer 344、棕色挪威大鼠和Lewis大鼠的体外淋巴细胞促凝反应。当用LPS体外刺激外周血单核细胞（PBM）时，通过加速重新钙化的人或大鼠少血小板血浆的凝固进行检测时，观察到了促凝活性（PCA）反应。反应迅速，在4小时达到最大值。5 mM的EDTA不能使PCA与活的PBM物理分离，这与存在内在质膜启动分子而非钙结合的含γ-羧基谷氨酸蛋白酶一致。用环己酰亚胺或放线菌素D孵育细胞可阻止单核细胞PCA的诱导，这表明存在新的生物合成需求。用华法林培养PBM不会降低效应器PCA的功能，维生素K也不会增强内毒素诱导的PCA的功能，这表明功能活性并非归因于含γ-羧基谷氨酸的蛋白质。丝氨酸蛋白酶抑制剂不会对细胞PCA分子产生抑制作用。LPS诱导的PCA似乎涉及一种组织因子样分子，因为介导PCA需要因子X和VII。从LPS刺激的PBM中分离单核细胞和T淋巴细胞表明，PCA存在于富含单核细胞部分。当将分离的大鼠T淋巴细胞和单核细胞分别暴露于LPS时，未诱导出PCA。相反，当细胞混合时，LPS诱导了PCA，这表明PCA反应涉及T淋巴细胞和单核细胞群体中细胞之间的细胞协作。
