Beezhold D H, Leftwich J A, Hall R E
Laboratory of Macrophage Biology, Guthrie Research Institute, Sayre, PA 18840-1692.
J Immunol. 1989 Nov 15;143(10):3217-21.
Bacterial products are potent stimulators of TNF and IL-1 release, however, the factors that regulate cytokine secretion in the absence of bacterial products are not well defined. P48 is a cytokine recently identified in the supernatant of the human null cell leukemia cell line Reh, which induces differentiation and cytolytic activity in HL-60 cells. P48 has been purified to homogeneity and is distinct from TNF-alpha TNF-beta, IFN-gamma, IL-6, and macrophage CSF. In the present study we examined the ability of P48 to stimulate cytokine release by human peripheral blood monocytes. P48 stimulated the secretion of TNF and IL-1 in a dose-dependent manner. Priming the monocytes with IFN-gamma enhanced P48-induced cytokine release but was not a requirement for secretion. Cytokine secretion was in response to P48 and was not caused by endotoxin contamination. The cytokine-inducing activity of P48 was extremely sensitive to heat treatment but could not be eliminated by using polymyxin B. Polyclonal antisera to P48 completely blocked the cytokine-inducing activity. P48 may be an important new member of the cytokine network involved in the regulation of cytokine secretion by monocytes.
细菌产物是肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）释放的强效刺激物，然而，在没有细菌产物的情况下调节细胞因子分泌的因素尚未明确界定。P48是最近在人无核细胞白血病细胞系Reh的上清液中鉴定出的一种细胞因子，它可诱导HL-60细胞分化和溶细胞活性。P48已被纯化至同质，且不同于肿瘤坏死因子-α（TNF-α）、肿瘤坏死因子-β（TNF-β）、干扰素-γ（IFN-γ）、白细胞介素-6（IL-6）和巨噬细胞集落刺激因子（macrophage CSF）。在本研究中，我们检测了P48刺激人外周血单核细胞释放细胞因子的能力。P48以剂量依赖的方式刺激TNF和IL-1的分泌。用IFN-γ预处理单核细胞可增强P48诱导的细胞因子释放，但不是分泌所必需的。细胞因子分泌是对P48的反应，而非由内毒素污染引起。P48的细胞因子诱导活性对热处理极为敏感，但不能通过使用多粘菌素B消除。针对P48的多克隆抗血清完全阻断了细胞因子诱导活性。P48可能是参与调节单核细胞分泌细胞因子的细胞因子网络中的一个重要新成员。
