Impaired lipid metabolism in idiopathic pulmonary alveolar proteinosis

Lipids in Health and Disease

Yuanjue Zhu¹  Yi Xiao¹  Wenbing Xu¹  Juan Wang¹  Yaosong Gui¹  Ruie Feng²  Jiong Zhou³  Lan Wang¹  Kai-Feng Xu¹  Jinmei Luo¹  Xinlun Tian¹ 

[1] Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China;Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China;Office for Infection Control, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

关键词: triglyceride;    pulmonary alveolar proteinosis;    lipid;    high-density lipoprotein cholesterol;   

Others  :  1212689
DOI  :  10.1186/1476-511X-10-54

 received in 2011-03-08, accepted in 2011-04-12,  发布年份 2011

【 摘 要 】

Background

It is well known that lipids abnormally accumulate in the alveoli during idiopathic pulmonary alveolar proteinosis (PAP). It is unclear, however, whether lipids also abnormally accumulate in serum. This study investigated the serum lipid panels in idiopathic PAP patients and explored the relationships between serum levels and the severity of idiopathic PAP.

Methods and Results

Clinical data including the level of serum lipids were evaluated in 33 non-diabetic idiopathic PAP patients and 157 healthy volunteers. Serum levels of triglyceride were higher in PAP patients than in healthy subjects (median: 192.00 mg/dl (P₂₅: 104.36, P₇₅: 219.00) vs 119.56 mg/dl (P₂₅: 78.81, P₇₅: 193.03), P < 0.05), while high-density lipoprotein cholesterol (HDL-C) levels were lower in patients than in the control group (42.50 ± 10.30 vs 51.34 ± 12.06 mg/dl, P < 0.01). Forced expiratory volume in one second and forced vital capacity in hypertriglyceridemia patients were lower than those in patients with normal triglyceride. Serum LDL-C and HDL-C ratio correlated negatively with PaO₂ (r = -0.403, P < 0.05) and positively with lactate dehydrogenase (r = 0.381, P < 0.05).

Conclusions

PAP associates with high triglyceride and low HDL levels in the serum, and these lipids provide potential intervention strategy for treatment.

【 授权许可】

   
2011 Tian et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Seymour JF, Presneill JJ: Pulmonary alveolar proteinosis progress in the first 44 years. Am J Respir Crit Care Med 2002, 166:215-235.
• [2]Trapnell BC, Whitsett JA, Nakata K: Pulmonary alveolar proteinosis. N Engl J Med 2003, 349:2527-2539.
• [3]Huizar I, Kavuru MS: Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management. Curr Opin Pulm Med 2009, 15:491-498.
• [4]Xie L, Zhao TM, Wang QY, Chen LA, Li AM, Wang DT, Qi F, Liu YN: Secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome. Chin Med J 2007, 120:1114-1116.
• [5]Batenburg JJ, Haagsman HP: The lipids of pulmonary surfactant: dynamics and interactions with proteins. Prog Lipid Res 1998, 37:235-276.
• [6]Meaney S, Bonfield TL, Hansson M, Babiker A, Kavuru MS, Thomassen MJ: Serum cholestenoic acid as a potential marker of pulmonary cholesterol homeostasis: increased levels in patients with pulmonary alveolar proteinosis. J Lipid Res 2004, 45:2354-2360.
• [7]Chinese committee of prevention and treatment of dyslipidemia in Chinese adults: Guideline of prevention and treatment of adult dyslipidemia in China. Chin J Cardiovasc Dis 2007, 35:390-419. (Chinese)
• [8]Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, ATS/ERS Task Force: Standardisation of spirometry. Eur Respir J 2005, 26:319-338.
• [9]Wanger J, Clausen JL, Coates A, Pederson OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G: Standardisation of the measurement of lung volumes. Eur Respir J 2005, 26:511-522.
• [10]Macintyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CP, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, Gustafsson P, Hankinson J, Jensen R, McKay R, Miller MR, Navajas D, Pedersen OF, Pellegrino R, Wanger J: Satndardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005, 26:720-735.
• [11]Zamanian RT, Hansmann G, Snook S, Lilienfeld D, Rappaport KM, Reaven GM, Rabinovitch M, Doyle RL: Insulin resistance in pulmonary arterial hypertension. Eur Respir J 2009, 33:318-324.
• [12]Huang SK, Peters-Golden M: Eicosanoid lipid mediators in fibrotic lung diseases: ready for prime time? Chest 2008, 133:1442-1450.
• [13]Kavuru MS, Sullivan EJ, Piccin R, Thomassen MJ, Stoller JK: Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis. Am J Respir Crit Care Med 2000, 161:1143-1148.
• [14]Inoue Y, Trapnell BC, Tazawa R, Arai T, Takada T, Hizawa N, Kasahara Y, Tatsumi K, Hojo M, Ichiwata T, Tanaka N, Yamaguchi E, Eda R, Oishi K, Tsuchihashi Y, Kaneko C, Nukiwa T, Sakatani M, Krischer JP, Nakata K, Japanese Center of the Rare Lung Diseases Consortium: Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med 2008, 177:752-762.
• [15]Sakagami T, Uchida K, Suzuki T, Carey BC, Wood RE, Wert SE, Whitsett JA, Trapnell BC, Luisetti M: Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis. N Engl J Med 2009, 361:2679-2681.
• [16]Yoshida M, Ikegami M, Reed JA, Chroneos ZC, Whitsett JA: GM-CSF regulates protein and lipid catabolism by alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2001, 280:L379-L386.
• [17]Robinson TE, Trapnell BC, Goris ML, Quittell LM, Cornfield DN: Quantitative analysis of longitudinal response to aerosolized GM-CSF in two adolescents with autoimmune pulmonary alveolar proteinosis. Chest 2009, 135:842-848.
• [18]Kavuru MS, Sullivan EJ, Piccin R, Thomassen MJ, Stoller JK: Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis. Am J Respir Crit Care Med 2000, 161:1143-1148.
• [19]Tazuwa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, Hizawa N, Kasahara Y, Tatsumi K, Hojo M, Ishii H, Yokoba M, Tanaka N, Yamaguchi E, Eda R, Tsuchihashi Y, Morimoto K, Akira M, Terada M, Otsuka J, Ebina M, Kaneko C, Nukiwa T, Krischer JP, Akazawa K, Nakata K: Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis. Am J Respir Crit Care Med 2010, 181:1345-1354.
• [20]Ishibashi T, Yokoyama K, Shindo J: Potent cholesterol-lowering effect by human granulocyte-macrophage colony-stimulating factor in rabbits. Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor. Arterioscler Thromb 1994, 14:1534-1541.
• [21]Hamilton JA: GM-CSF in inflammation and autoimmunity. Trends Immunol 2002, 23:403-408.
• [22]Hotamisligil GS: Inflammation and metabolic disorders. Nature 2006, 444:860-867.
• [23]Popa C, Netea MG, van Riel PL, van der Meer JW, Stalenhoef AF: The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 2007, 48:751-762.
• [24]Hermus AR, Sweep CG, Demacker PN, van der Meer MJ, Kloppenborg PW, van der Meer JW: Continuous infusion of interleukin-1 beta in rats induces a profound fall in plasma levels of cholesterol and triglycerides. Arterioscler Thromb 1992, 12:1036-1043.
• [25]Bonfield TL, Farver CF, Barna BP, Malur A, Abraham S, Raychaudhuri B, Kavuru MS, Thomassen MJ: Peroxisome proliferator-activated receptor-gamma is deficient in alveolar macrophages from patients with alveolar proteinosis. Am J Respir Cell Mol Biol 2003, 29:677-682.
• [26]Malur A, Baker AD, McCoy AJ, Wells G, Barna BP, Kavuru MS, Malur AG, Thomassen MJ: Restoration of PPAR-γ reverses lipid accumulation in alveolar macrophages of GM-CSF knockout mice. Am J Physiol Lung Cell Mol Physiol 2011, 300:L73-L80.
• [27]Thomassen MJ, Barna BP, Malur AG, Bonfield TL, Farver CF, Malur A, Dalrymple H, Kavuru MS, Febbraio M: ABCG1 is deficient in alveolar macrophages of GM-CSF knockout mice and patients with pulmonary alveolar proteinosis. J Lipid Res 2007, 48:2762-2768.
• [28]Rotondo D, Davidson J: Prostaglandin and PPAR control of immune cell function. Immunology 2002, 105:20-22.
• [29]Touyz RM, Schiffrin EL: Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications. Vascul Pharmacol 2006, 45:19-28.
• [30]Henry RR, Lincoff AM, Mudaliar S: Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet 2009, 374:126-135.
• [31]Xu KF, Chen Y, Guo ZJ, Zhu YJ: Autoantibody against granulocyte macrophage colony- stimulating factor and other serum markers in pulmonary alveolar proteinosis. Zhonghua Jie He He Hu Xi Za Zhi 2004, 27:824-8. (Chinese)