Severely reduced neutrophil adhesion and impaired host defense against fecal and commensal bacteria in CD18-/- P-selectin-/- double null mice
Severely reduced neutrophil adhesion and impaired host defense against fecal and commensal bacteria in CD18-/- P-selectin-/- double null mice
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DOI：
10.1096/fj.02-0230com
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发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
Ley, K
中科院分区：
文献类型：
--
作者：
Forlow, SB;Foley, PL;Ley, K
白细胞募集到炎症部位需要选择子和整合素的功能。在某些炎症模型中，P选择素缺失（CD 62 P- /-）小鼠显示出轻度的中性粒细胞募集缺陷，而CD 18缺失（CD 18/-）小鼠显示出更严重的中性粒细胞募集缺陷。为了研究CD 18整合素和P-选择素在介导中性粒细胞募集中可能的合作相互作用，我们产生了CD 18- /-CD 62 P- /-双无效小鼠。CD 18/-CD 62 P/-小鼠在断奶和生育时明显正常，但后来体重增加失败，对粪便和肠道细菌感染的易感性增加，仅存活5-6个月。一些CD 18-/-CD 62 P-/-小鼠显示严重的自发性皮肤病变;大多数显示肺和肝脏中的中性粒细胞浸润，以及内脏的细菌培养阳性。CD 18-/-CD 62 P-/-小鼠经肿瘤坏死因子a处理后，其微静脉中滚动的白细胞数量和速度与野生型小鼠相似，但中性粒细胞粘附严重减少。在CD 18-/-CD 62 P-/小鼠中，只有25%的粘附白细胞是中性粒细胞，而在野生型、CD 62 P-/-和CD 18-/-单突变体中>90%。我们的数据表明，从小鼠中去除P-选择素和CD 18整合素会导致严重的中性粒细胞募集缺陷和自发性病理学。
Leukocyte recruitment to sites of inflammation requires the functions of selectors and integrins. P-selector null (CD62P- /-) mice show a mild and CD18 null (CD18 /-) mice a more severe neutrophil recruitment defect in some inflammatory models. To investigate the possible cooperative interactions between CD18 integrins and P-selector in mediating neutrophil recruitment, we generated CD18 - /- CD62P - /- double null mice. CD18 /- CD62P /- mice were apparently normal at weaning and fertile but later failed to gain weight, showed increased susceptibility to infection by fecal and commensal bacteria, and survived only 5-6 months. Some CD18-/-CD62P-/- mice showed severe spontaneous skin lesions; most showed neutrophil infiltration in the lungs and liver, and positive bacterial cultures from internal organs. The number and velocity of rolling leukocytes in tumor necrosis factor a treated venules of CD18-/-CD62P-/- mice was similar to those in wild-type mice, but neutrophil adhesion was severely reduced. Only 25% of adhered leukocytes were neutrophils in CD18-/-CD62P-/mice vs. >90% in wild-type, CD62P-/-, and CD18-/- single mutants. Our data show that removing both P-selectin and CD18 integrins from mice leads to severe neutrophil recruitment defects and spontaneous pathology.