生物谷報(bào)道：當(dāng)你吸入含有氧化物的污染空氣和煙草煙霧后,它將會(huì)導(dǎo)致你的肺的損傷,而且會(huì)促進(jìn)諸如哮喘和慢性阻塞性肺病(COPD)的產(chǎn)生.在«臨床調(diào)查雜志»的三月號(hào)上刊登的一項(xiàng)研究中,來自波士頓的哈佛公共衛(wèi)生學(xué)院的研究員們,認(rèn)識(shí)到老鼠通過一種新的機(jī)制來保護(hù)自己免受吸入氧化物的危害.
Lester Kobzik和他的同事們觀察到,對(duì)臭氧所致肺損傷有抵抗力的老鼠體內(nèi)的肺臟的免疫細(xì)胞(又稱為肺泡巨噬細(xì)胞)比那些對(duì)臭氧所致肺損傷敏感的老鼠的肺泡巨噬細(xì)胞要表達(dá)更多的蛋白質(zhì),這種蛋白質(zhì)被稱為MARCO.
與MARCO所扮演的保護(hù)肺臟免受氧化物所致?lián)p傷的角色一致,缺乏MARCO的老鼠較表達(dá)正常MARCO的老鼠無論暴露在臭氧還是在其它氧化物之下,都表現(xiàn)出更多的肺損傷. MARCO提供保護(hù)的原因是它促使肺泡巨噬細(xì)胞吸收那些被氧化物修飾過的脂質(zhì),而這些脂質(zhì)如果不清除的話將會(huì)引發(fā)一個(gè)炎癥反應(yīng).
在清除那些肺臟中被氧化物修飾過的脂質(zhì)方面有相似作用的另一種MARCO相關(guān)蛋白質(zhì), SR-AI/II,已經(jīng)被鑒定出來了.
正如Birmingham城的Alabama大學(xué)的Edward Postlethwait所寫的一篇附隨的評(píng)論中討論的一樣,現(xiàn)在非常重要的是確定在人體內(nèi),這些相似的功能是否應(yīng)該歸因于這些或其它相關(guān)蛋白質(zhì)(它們總稱為清除劑受體),原因是諸如哮喘和COPD的肺臟疾病有著巨大的發(fā)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.
原文出處：
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]
背景知識(shí)：
COPD：
%606963
PULMONARY DISEASE, CHRONIC OBSTRUCTIVE, SEVERE EARLY-ONSET
Gene map locus 14q32.1, 11q22-q23, 2q
相關(guān)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
作者簡(jiǎn)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.
