Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung injury

Respiratory Research

Ralph C Schimmer⁴  Christa Booy³  Livia Reyes¹  Thomas Pasch³  Reto Schwendener²  Beatrice Beck-Schimmer¹ 

[1] Institute of Physiology, University of Zurich, Switzerland;Paul Scherrer Institute, Villigen, Switzerland;Institute of Anesthesiology, University of Zurich, Switzerland;Department of Surgery, University of Zurich, Switzerland

关键词: monocyte chemoattractant protein-1;    macrophage depletion;    lung inflammation;    lipopolysaccharide;    effector cells;   

Others  :  1227284
DOI  :  10.1186/1465-9921-6-61

 received in 2004-07-25, accepted in 2005-06-22,  发布年份 2005

【 摘 要 】

Background

Alveolar macrophages play an important role during the development of acute inflammatory lung injury. In the present study, in vivo alveolar macrophage depletion was performed by intratracheal application of dichloromethylene diphosphonate-liposomes in order to study the role of these effector cells in the early endotoxin-induced lung injury.

Methods

Lipopolysaccharide was applied intratracheally and the inflammatory reaction was assessed 4 hours later. Neutrophil accumulation and expression of inflammatory mediators were determined. To further analyze in vivo observations, in vitro experiments with alveolar epithelial cells and alveolar macrophages were performed.

Results

A 320% increase of polymorphonuclear leukocytes in bronchoalveolar lavage fluid was observed in macrophage-depleted compared to macrophage-competent lipopolysaccharide-animals. This neutrophil recruitment was also confirmed in the interstitial space. Monocyte chemoattractant protein-1 concentration in bronchoalveolar lavage fluid was significantly increased in the absence of alveolar macrophages. This phenomenon was underlined by in vitro experiments with alveolar epithelial cells and alveolar macrophages. Neutralizing monocyte chemoattractant protein-1 in the airways diminished neutrophil accumulation.

Conclusion

These data suggest that alveolar macorphages play an important role in early endotoxin-induced lung injury. They prevent neutrophil influx by controlling monocyte chemoattractant protein-1 production through alveolar epithelial cells. Alveolar macrophages might therefore possess robust anti-inflammatory effects.

【 授权许可】

   
2005 Beck-Schimmer et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Beck-Schimmer B, Schimmer RC, Warner RL, Schmal H, Nordblom G, Flory CM, Lesch ME, Friedl HP, Schrier DJ, Ward PA: Expression of lung vascular and airway ICAM-1 after exposure to bacterial lipopolysaccharide. Am J Respir Cell Mol Biol 1997, 17:344-352.
• [2]Li XY, Donaldson K, MacNee W: Lipopolysaccharide-induced alveolar epithelial permeability: the role of nitric oxide. Am J Respir Crit Care Med 1998, 157:1027-1033.
• [3]Madjdpour C, Oertli B, Ziegler U, Bonvini JM, Pasch T, Beck-Schimmer B: Lipopolysaccharide induces functional ICAM-1 expression in rat alveolar epithelial cells in vitro. Am J Physiol Lung Cell Mol Physiol 2000, 278:L572-9.
• [4]Sibille Y, Reynolds HY: Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Respir Dis 1990, 141:471-501.
• [5]Monton C, Torres A: Lung inflammatory response in pneumonia. Monaldi Arch Chest Dis 1998, 53:56-63.
• [6]Gonzalez-Amaro R, Diaz-Gonzalez F, Sanchez-Madrid F: Adhesion molecules in inflammatory diseases. Drugs 1998, 56:977-988.
• [7]Beck-Schimmer B, Schimmer RC, Madjdpour C, Bonvini JM, Pasch T, Ward PA: Hypoxia mediates increased neutrophil and macrophage adhesiveness to alveolar epithelial cells. Am J Respir Cell Mol Biol 2001, 25:780-787.
• [8]Paine R, Rolfe MW, Standiford TJ, Burdick MD, Rollins BJ, Strieter RM: MCP-1 expression by rat type II alveolar epithelial cells in primary culture. J Immunol 1993, 150:4561-4570.
• [9]Thepen T, Van Rooijen N, Kraal G: Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J Exp Med 1989, 170:499-509.
• [10]Roscic-Mrkic B, Schwendener RA, Odermatt B, Zuniga A, Pavlovic J, Billeter MA, Cattaneo R: Roles of macrophages in measles virus infection of genetically modified mice. J Virol 2001, 75:3343-3351.
• [11]Goldblum SE, Wu KM, Jay M: Lung myeloperoxidase as a measure of pulmonary leukostasis in rabbits. Journal of Applied Physiology 1985, 59:1978-1985.
• [12]Beck-Schimmer B, Madjdpour C, Kneller S, Ziegler U, Pasch T, Wuethrich RP, Ward PA, Schimmer RC: Role of alveolar epithelial ICAM-1 in lipopolysachharide-induced lung inflammation. Eur Resp J 2002, 19:1142-1150.
• [13]Kamp DW, Dunn MM, Sbalchiero JS, Knap AM, Weitzman SA: Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced pulmonary epithelial cell injury. Am J Physiol 1994, 266:L84-91.
• [14]Fox SE, Lu W, Maheshwari A, Christensen RD, Calhoun DA: The effects and comparative differences of neutrophil specific chemokines on neutrophil chemotaxis of the neonate. Cytokine 2005, 29:135-140.
• [15]Madjdpour C, Jewell UR, Kneller S, Ziegler U, Schwendener R, Booy C, Klausli L, Pasch T, Schimmer RC, Beck-Schimmer B: Decreased alveolar oxygen induces lung inflammation. Am J Physiol Lung Cell Mol Physiol 2003, 284:L360-7.
• [16]Lentsch AB, Czermak BJ, Bless NM, Van Rooijen N, Ward PA: Essential role of alveolar macrophages in intrapulmonary activation of NF-kappaB. Am J Respir Cell Mol Biol 1999, 20:692-698.
• [17]Broug-Holub E, Toews GB, van Iwaarden JF, Strieter RM, Kunkel SL, Paine R, Standiford TJ: Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia: elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival. Infect Immun 1997, 65:1139-1146.
• [18]Fels AO, Cohn ZA: The alveolar macrophage. J Appl Physiol 1986, 60:353-369.
• [19]Kradin RL, Liu HW, van Rooijen N, Springer K, Zhao LH, Leary CP: Pulmonary immunity to Listeria is enhanced by elimination of alveolar macrophages. Am J Respir Crit Care Med 1999, 159:1967-1974.
• [20]Ulich TR, Howard SC, Remick DG, Wittwer A, Yi ES, Yin S, Guo K, Welply JK, Williams JH: Intratracheal administration of endotoxin and cytokines. VI. Antiserum to CINC inhibits acute inflammation. Am J Physiol 1995, 268:L245-50.
• [21]Koay MA, Gao X, Washington MK, Parman KS, Sadikot RT, Blackwell TS, Christman JW: Macrophages are necessary for maximal nuclear factor-kappa B activation in response to endotoxin. Am J Respir Cell Mol Biol 2002, 26:572-578.
• [22]Hashimoto S, Pittet JF, Hong K, Folkesson H, Bagby G, Kobzik L, Frevert C, Watanabe K, Tsurufuji S, Wiener-Kronish J: Depletion of alveolar macrophages decreases neutrophil chemotaxis to Pseudomonas airspace infections. Am J Physiol 1996, 270:L819-28.
• [23]Johnston B, Burns AR, Suematsu M, Issekutz TB, Woodman RC, Kubes P: Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. J Clin Invest 1999, 103:1269-1276.
• [24]Ferrero E, Biswas P, Vettoretto K, Ferrarini M, Uguccioni M, Piali L, Leone BE, Moser B, Rugarli C, Pardi R: Macrophages exposed to Mycobacterium tuberculosis release chemokines able to recruit selected leucocyte subpopulations: focus on gammadelta cells. Immunology 2003, 108:365-374.
• [25]Watanabe T, Higuchi K, Hamaguchi M, Shiba M, Tominaga K, Fujiwara Y, Matsumoto T, Arakawa T: Monocyte chemotactic protein-1 regulates leukocyte recruitment during gastric ulcer recurrence induced by tumor necrosis factor-alpha. Am J Physiol Gastrointest Liver Physiol 2004, 287:G919-28.
• [26]Vozzelli MA, Mason SN, Whorton MH, Auten RLJ: Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung. Am J Physiol Lung Cell Mol Physiol 2004, 286:L488-93.
• [27]Maus U, Huwe J, Maus R, Seeger W, Lohmeyer J: Alveolar JE/MCP-1 and endotoxin synergize to provoke lung cytokine upregulation, sequential neutrophil and monocyte influx, and vascular leakage in mice. Am J Respir Crit Care Med 2001, 164:406-411.
• [28]Maus UA, Koay MA, Delbeck T, Mack M, Ermert M, Ermert L, Blackwell TS, Christman JW, Schlondorff D, Seeger W, Lohmeyer J: Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice. Am J Physiol Lung Cell Mol Physiol 2002, 282:L1245-52.
• [29]Beck-Schimmer B, Ortli B, Pasch T, Wüthrich RP: Hyaluronan induces monocyte chemoattractant protein-1 expression in renal tubular epithelial cells. Jornal of the American Society of Nephrology 1998, 9:2283-2290.
• [30]Fujii T, Hayashi S, Hogg JC, Mukae H, Suwa T, Goto Y, Vincent R, van Eeden SF: Interaction of alveolar macrophages and airway epithelial cells following exposure to particulate matter produces mediators that stimulate the bone marrow. Am J Respir Cell Mol Biol 2002, 27:34-41.
• [31]Berg JT, White JE, Tsan MF: Response of alveolar macrophage-depleted rats to hyperoxia. Exp Lung Res 1995, 21:175-185.
• [32]Xing Z, Jordana M, Kirpalani H, Driscoll KE, Schall TJ, Gauldie J: Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-alpha, macrophage inflammatory protein-2, interleukin-1 beta, and interleukin-6 but not RANTES or transforming growth factor-beta 1 mRNA expression in acute lung inflammation. Am J Respir Cell Mol Biol 1994, 10:148-153.
• [33]Franke-Ullmann G, Pfortner C, Walter P, Steinmuller C, Lohmann-Matthes ML, Kobzik L: Characterization of murine lung interstitial macrophages in comparison with alveolar macrophages in vitro. J Immunol 1996, 157:3097-3104.
• [34]Xing Z, Kirpalani H, Torry D, Jordana M, Gauldie J: Polymorphonuclear leukocytes as a significant source of tumor necrosis factor-alpha in endotoxin-challenged lung tissue. Am J Pathol 1993, 143:1009-1015.