Medeiros A I, Malheiro A, Jose P J, Conroy D M, Williams T J, Faccioli L H
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Inflamm Res. 2004 Aug;53(8):351-4. doi: 10.1007/s00011-004-1269-x. Epub 2004 Aug 10.
In the present study, we evaluated the levels of MIP-1alpha and eotaxin and in vivo migration in the peritoneal cavity model, in mice inoculated with live yeast forms of Histoplasma capsulatum or the beta-glucan cell wall component of this fungus, and the influence of a leukotriene biosynthesis inhibitor, MK886, on the release of these chemokines in relation to cell recruitment.
Female outbred Swiss mice (N = 4-5 per group, 3-4 wk, were used. Mice were injected i.p. with 1 ml of the 6 x 10(5) live yeast form of the fungus or with 10 microg of beta-glucan from the cell wall fraction, and treated daily with MK886 (1 mg kg(-1), p.o.) or vehicle.
The fungus induced rapid generation of high levels of MIP-1alpha, which remained elevated from 4-48 h whereas very little eotaxin was detected at any time point (Fig. 1A and B). In contrast, the beta-glucan induced a little MIP-1alpha but considerably higher concentrations of eotaxin within the first four hours; however, the level of neither chemokine was sustained (Fig. 2A and B). Treatment of animals with MK886 was effective in reducing the numbers of neutrophils, eosinophils and, to a lesser degree, mononuclear cells accumulating in the peritoneal cavity in response to both the live fungus (Fig. 1C-E) and the cell wall beta-glucan (Fig. 2C-E).
The results suggest that chemokines and leukotrienes may play key roles in the inflammatory cell influx to H. capsulatum infection or to the inoculation of the beta-glucan cell wall component of this fungus
在本研究中，我们评估了接种荚膜组织胞浆菌活酵母形式或该真菌的β-葡聚糖细胞壁成分的小鼠腹腔模型中MIP-1α和嗜酸性粒细胞趋化因子的水平以及体内迁移情况，以及白三烯生物合成抑制剂MK886对这些趋化因子释放与细胞募集相关的影响。
使用雌性远交瑞士小鼠（每组4-5只，3-4周龄）。小鼠腹腔注射1 ml含6×10⁵个真菌活酵母形式的溶液或10 μg来自细胞壁部分的β-葡聚糖，并每日用MK886（1 mg kg⁻¹，口服）或赋形剂处理。
真菌诱导快速产生高水平的MIP-1α，在4-48小时内一直保持升高，而在任何时间点检测到的嗜酸性粒细胞趋化因子都很少（图1A和B）。相比之下，β-葡聚糖在最初四小时内诱导产生少量MIP-1α但嗜酸性粒细胞趋化因子浓度高得多；然而，两种趋化因子的水平都没有持续（图2A和B）。用MK886处理动物可有效减少因活真菌（图1C-E）和细胞壁β-葡聚糖（图2C-E）而在腹腔中积聚的中性粒细胞、嗜酸性粒细胞以及程度较轻的单核细胞数量。
结果表明趋化因子和白三烯可能在炎症细胞流入荚膜组织胞浆菌感染或该真菌的β-葡聚糖细胞壁成分接种中起关键作用。
