George Caroline L S, Goss Kelli L, Meyerholz David K, Lamb Fred S, Snyder Jeanne M
Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Infect Immun. 2008 Jan;76(1):380-90. doi: 10.1128/IAI.01043-07. Epub 2007 Oct 29.
The collectins surfactant-associated protein A (SP-A) and SP-D are components of innate immunity that are present before birth. Both proteins bind pathogens and assist in clearing infection. The significance of SP-A and SP-D as components of the neonatal immune system has not been investigated. To determine the role of SP-A and SP-D in neonatal immunity, wild-type, SP-A null, and SP-D null mice were bred in a bacterium-laden environment (corn dust bedding) or in a semisterile environment (cellulose fiber bedding). When reared in the corn dust bedding, SP-A null pups had significant mortality (P < 0.001) compared to both wild-type and SP-D null pups exposed to the same environment. The mortality of the SP-A null pups was associated with significant gastrointestinal tract pathology but little lung pathology. Moribund SP-A null newborn mice exhibited Bacillus sp. and Enterococcus sp. peritonitis. When the mother or newborn produced SP-A, newborn survival was significantly improved (P < 0.05) compared to the results when there was a complete absence of SP-A in both the mother and the pup. Significant sources of SP-A likely to protect a newborn include the neonatal lung and gastrointestinal tract but not the lactating mammary tissue of the mother. Furthermore, exogenous SP-A delivered by mouth to newborn SP-A null pups with SP-A null mothers improved newborn survival in the corn dust environment. Therefore, a lack of SP-D did not affect newborn survival, while SP-A produced by either the mother or the pup or oral exogenous SP-A significantly reduced newborn mortality associated with environmentally induced infection in SP-A null newborns.
凝集素表面活性剂相关蛋白A(SP-A)和SP-D是先天免疫的组成部分,在出生前就已存在。这两种蛋白都能结合病原体并协助清除感染。SP-A和SP-D作为新生儿免疫系统组成部分的意义尚未得到研究。为了确定SP-A和SP-D在新生儿免疫中的作用,将野生型、SP-A基因敲除和SP-D基因敲除小鼠饲养在充满细菌的环境(玉米粉尘垫料)或半无菌环境(纤维素纤维垫料)中。当饲养在玉米粉尘垫料中时,与暴露于相同环境的野生型和SP-D基因敲除幼崽相比,SP-A基因敲除幼崽的死亡率显著升高(P<0.001)。SP-A基因敲除幼崽的死亡与严重的胃肠道病理改变有关,但肺部病理改变较轻。濒死的SP-A基因敲除新生小鼠表现出芽孢杆菌属和肠球菌属腹膜炎。当母亲或新生儿产生SP-A时,与母亲和幼崽均完全缺乏SP-A的情况相比,新生儿存活率显著提高(P<0.05)。可能保护新生儿的SP-A的重要来源包括新生儿的肺和胃肠道,但不包括母亲的泌乳乳腺组织。此外,给母亲为SP-A基因敲除的新生SP-A基因敲除幼崽经口给予外源性SP-A可提高其在玉米粉尘环境中的存活率。因此,缺乏SP-D并不影响新生儿存活,而母亲或幼崽产生SP-A或经口给予外源性SP-A可显著降低SP-A基因敲除新生儿因环境诱导感染而导致的死亡率。