生物谷报道：当你吸入含有氧化物的污染空气和烟草烟雾后,它将会导致你的肺的损伤,而且会促进诸如哮喘和慢性阻塞性肺病(COPD)的产生.在«临床调查杂志»的三月号上刊登的一项研究中,来自波士顿的哈佛公共卫生学院的研究员们,认识到老鼠通过一种新的机制来保护自己免受吸入氧化物的危害.
Lester Kobzik和他的同事们观察到,对臭氧所致肺损伤有抵抗力的老鼠体内的肺脏的免疫细胞(又称为肺泡巨噬细胞)比那些对臭氧所致肺损伤敏感的老鼠的肺泡巨噬细胞要表达更多的蛋白质,这种蛋白质被称为MARCO.
与MARCO所扮演的保护肺脏免受氧化物所致损伤的角色一致,缺乏MARCO的老鼠较表达正常MARCO的老鼠无论暴露在臭氧还是在其它氧化物之下,都表现出更多的肺损伤. MARCO提供保护的原因是它促使肺泡巨噬细胞吸收那些被氧化物修饰过的脂质,而这些脂质如果不清除的话将会引发一个炎症反应.
在清除那些肺脏中被氧化物修饰过的脂质方面有相似作用的另一种MARCO相关蛋白质, SR-AI/II,已经被鉴定出来了.
正如Birmingham城的Alabama大学的Edward Postlethwait所写的一篇附随的评论中讨论的一样,现在非常重要的是确定在人体内,这些相似的功能是否应该归因于这些或其它相关蛋白质(它们总称为清除剂受体),原因是诸如哮喘和COPD的肺脏疾病有着巨大的发病率.
Figure 1
Ozone upregulates MARCO in lungs from ozone-resistant HeJ mice. HeJ or congenic ozone-sensitive OuJ mice were exposed to 0.3 ppm ozone for up to 48 hours. Microarray analysis (A) and RT-PCR (B) were performed on total RNA isolated from lung samples and showed increased MARCO mRNA expression in HeJ mice (filled symbols) compared with OuJ mice (open symbols). (C) Western blot analysis of lung tissue obtained after 48 hours of ozone exposure also showed increased MARCO protein expression. (D) Ozone upregulates MARCO on the surface of AMs of C57BL/6 mice exposed to 0.3 ppm ozone for 48 hours, as shown by increased fluorescence after flow cytometric analysis. Results shown are representative of 3 independent experiments. MFI, mean fluorescence intensity. *P < 0.05 versus ozone-treated OuJ; #P < 0.05 versus air-exposed control.
原文出处：
Journal of Clinical Investigation March 1 2007, Volume 117, Issue 3
Morten Dahl, Alison K. Bauer, Mohamed Arredouani, Raija Soininen, Karl Tryggvason, Steven R. Kleeberger, and Lester Kobzik
Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II
J. Clin. Invest. 2007 117: 757-764. [Abstract] [Full Text] [PDF]
背景知识：
COPD：
%606963
PULMONARY DISEASE, CHRONIC OBSTRUCTIVE, SEVERE EARLY-ONSET
Gene map locus 14q32.1, 11q22-q23, 2q
相关基因：
Marco
Official Symbol: Marco and Name: macrophage receptor with collagenous structure [Mus musculus]
Other Aliases: AI323439, Ly112, Scara2
Chromosome: 1; Location: 1 E4-F
GeneID: 17167
MARCO
Official Symbol: MARCO and Name: macrophage receptor with collagenous structure [Homo sapiens]
Other Aliases: SCARA2
Other Designations: scavenger receptor class A, member 2
Chromosome: 2; Location: 2q12-q13
MIM: 604870
GeneID: 8685
Msr1
Official Symbol: Msr1 and Name: macrophage scavenger receptor 1 [Mus musculus]
Other Aliases: MSR, MSR-A, SR-AI, SR-AII, Scara1, Scvr
Other Designations: scavenger receptor
Chromosome: 8; Location: 8 20.0 cM
GeneID: 20288
作者简介：
Lester Kobzik
Professor in the Department of Environmental Health
Department of Environmental Health
Other Affiliations
Professor of Pathology, HMS
Pathologist, Brigham & Women's Hospital
Education
M.D., 1979, Tufts University School of Medicine
Research Interests
My main research interest is how the lung interacts with inhaled particles—be they environmental particulates, pathogens or allergens. One focus is the role of the lung macrophage in lung defense mechanisms and pulmonary inflammation, especially in relationship to environmental lung disease. A fascinating aspect of lung macrophages is their selective interaction with inhaled particles. They respond with simple ingestion and clearance to some particles (the harmless, 'inert' dusts). In contrast, encounters of lung macrophages with pathogenic particles result in release of mediators that initiate inflammation and injury. These mysteriously regulated responses are central to the public health problems caused by air pollution in urban areas, by dusts in certain occupations, and by certain inhaled pathogenic organisms. My lab is approaching the problem at a number of levels. I have used in vitro analysis of macrophage-particle interactions to identify features of both host (e.g., inflammatory priming) and particle (e.g., solid vs. soluble phases, trace endotoxin) important in pathogenesis. To identify the structure(s) that mediate particle binding, my lab has used monoclonal antibodies and expression cloning to implicate scavenger-type receptors on the cell surface of the lung macrophage as the molecules that allow this cell to bind a diverse range of inert particles. Recently, we have found that a surprising member of this family of receptors (MARCO) is responsible for this important macrophage function. Current studies using ‘knockout’ mice deficient in scavenger receptors confirm their critical importance in defense of the lung against environmental particles and infectious bacteria. My research program is also targeting another problem caused by inhaled particles (allergens)—asthma. Specifically, these studies have developed a novel mouse model of the maternal transmission of asthma risk. The role of maternal lymphocytes and cytokines is being investigated using adoptive transfer and cytokine blockade technologies. The goal is to provide new insights into the mechanisms for allergic or ‘tolerance’ responses to inhaled allergens in early life.
select Publications
Arredouani M, Yang Z, Ning Y, Qin G, Soininen R, Tryggvason K, Kobzik L. The scavenger receptor MARCO Is required for lung defense against pneumococcal pneumonia and inhaled particles. J Exp Med. 2004;200:267-72.
Arredouani MS, Palecanda A, Koziel H, Huang YC, Imrich A, Sulahian TH, Ning YY, Yang Z, Pikkarainen T, Sankala M, Vargas SO, Takeya M, Tryggvason K, Kobzik L. MARCO is the major binding receptor for unopsonized particles and bacteria on human alveolar macrophages. J Immunol. 2005;175:6058-64.
Jozefowski S, Arredouani M, Sulahian T, Kobzik L. Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO. J Immunol. 2005;175:8032-41.
Leme AS, Hubeau C, Xiang Y, Goldman A, Hamada K, Suzaki Y, Kobzik L. Role of breast milk in a mouse model of maternal transmission of asthma susceptibility. J Immunol. 2006;176:762-9.
Hubeau C, Apostolou I, Kobzik L. Adoptively-transferred allergen-specific T cells cause maternal transmission of asthma risk. Am J Pathol. 2006;168:1931-1939.
