Published ahead of print on September 25, 2002, doi:10.1164/rccm.200207-698OC
American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 171-179, (2003)
© 2003 American Thoracic Society
Alveolar Macrophages Have a Protective Antiinflammatory Role during Murine Pneumococcal Pneumonia
Sylvia Knapp,
Jaklien C. Leemans,
Sandrine Florquin,
Judith Branger,
Nico A. Maris,
Jennie Pater,
Nico van Rooijen and
Tom van der Poll
Laboratory of Experimental Internal Medicine, Departments of Pathology and Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam; and Department of Cell Biology and Immunology, Free University Amsterdam, Amsterdam, The Netherlands
Correspondence and requests for reprints should be addressed to Sylvia Knapp, M.D., Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-132, 1105 AZ Amsterdam, The Netherlands. E-mail: s.knapp{at}amc.uva.nl
Alveolar macrophages (AMs) are considered major effector cells in host defense against respiratory tract infections by virtue of their potent phagocytic properties. In addition, AMs may regulate the host inflammatory response to infection by production of cytokines and by their capacity to phagocytose apoptotic polymorphonuclear cells (PMNs). To elucidate the in vivo contribution of AM to host defense against pneumococcal pneumonia, we depleted mice of AMs via pulmonary application of liposomal dichloromethylene-bisphosphonate (AM- mice) before inoculation with Streptococcus pneumoniae; control mice received saline (AM+sal) or liposomal phosphate-buffered saline (AM+lip) before bacterial inoculation. AM- mice displayed a significantly higher mortality compared with AM+ control mice, whereas bacterial clearance did not differ. Poor outcome of AM- mice was accompanied by a pronounced increase of local proinflammatory cytokine production as well as strongly elevated and prolonged pulmonary PMN accumulation. Closer examination of infiltrating PMN in AM- mice disclosed high proportions of apoptotic and secondary necrotic cells, reflecting the lack of efficient clearance mechanisms in the absence of AMs. Furthermore, caspase-3 staining showed only slightly higher activity in AM- mice, arguing against accelerated apoptosis per se. These data suggest that AMs are indispensable in the host response to pneumococcal pneumonia by means of their capacity to modulate inflammation, possibly via elimination of apoptotic PMNs.
Key Words: bacterial • lung • macrophage • inflammation • apoptosis
This article has been cited by other articles:
|
|
|
|
 
M. A.D. van Zoelen, S. Florquin, R. de Beer, J. M. Pater, M. I. Verstege, J. C.M. Meijers, and T. van der Poll
Urokinase Plasminogen Activator Receptor-Deficient Mice Demonstrate Reduced Hyperoxia-Induced Lung Injury
Am. J. Pathol.,
June 1, 2009;
174(6):
2182 - 2189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Li, Y. Jia, M. Pichavant, F. Loison, B. Sarraj, A. Kasorn, J. You, B. E. Robson, D. T. Umetsu, J. P. Mizgerd, et al.
Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia
Blood,
May 14, 2009;
113(20):
4930 - 4941.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Winter, W. Herbold, R. Maus, F. Langer, D. E. Briles, J. C. Paton, T. Welte, and U. A. Maus
Important Role for CC Chemokine Ligand 2-Dependent Lung Mononuclear Phagocyte Recruitment to Inhibit Sepsis in Mice Infected with Streptococcus pneumoniae
J. Immunol.,
April 15, 2009;
182(8):
4931 - 4937.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tian, S. Weber, P. Thorkildson, T. R. Kozel, and L.-a. Pirofski
Efficacy of Opsonic and Nonopsonic Serotype 3 Pneumococcal Capsular Polysaccharide-Specific Monoclonal Antibodies against Intranasal Challenge with Streptococcus pneumoniae in Mice
Infect. Immun.,
April 1, 2009;
77(4):
1502 - 1513.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Boelen, J. Kwakkel, C. W. Wieland, D. L. St. Germain, E. Fliers, and A. Hernandez
Impaired Bacterial Clearance in Type 3 Deiodinase-Deficient Mice Infected with Streptococcus pneumoniae
Endocrinology,
April 1, 2009;
150(4):
1984 - 1990.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Xu, D. Droemann, J. Rupp, H. Shen, X. Wu, T. Goldmann, S. Hippenstiel, P. Zabel, and K. Dalhoff
Modulation of the Inflammatory Response to Streptococcus pneumoniae in a Model of Acute Lung Tissue Infection
Am. J. Respir. Cell Mol. Biol.,
November 1, 2008;
39(5):
522 - 529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Bem, A. W. Farnand, V. Wong, A. Koski, M. E. Rosenfeld, N. van Rooijen, C. W. Frevert, T. R. Martin, and G. Matute-Bello
Depletion of resident alveolar macrophages does not prevent Fas-mediated lung injury in mice
Am J Physiol Lung Cell Mol Physiol,
August 1, 2008;
295(2):
L314 - L325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-C. Lu, H.-C. Lai, S.-C. Hsieh, and J.-K. Chen
Resveratrol ameliorates Serratia marcescens-induced acute pneumonia in rats
J. Leukoc. Biol.,
April 1, 2008;
83(4):
1028 - 1037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Nieminen, C. St-Pierre, P. Bhaumik, F. Poirier, and S. Sato
Role of Galectin-3 in Leukocyte Recruitment in a Murine Model of Lung Infection by Streptococcus pneumoniae
J. Immunol.,
February 15, 2008;
180(4):
2466 - 2473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Wosten-van Asperen, R. Lutter, J. J. Haitsma, M. P. Merkus, J. B. van Woensel, C. M. van der Loos, S. Florquin, B. Lachmann, and A. P. Bos
ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin
Eur. Respir. J.,
February 1, 2008;
31(2):
363 - 371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Taut, C. Winter, D. E. Briles, J. C. Paton, J. W. Christman, R. Maus, R. Baumann, T. Welte, and U. A. Maus
Macrophage Turnover Kinetics in the Lungs of Mice Infected with Streptococcus pneumoniae
Am. J. Respir. Cell Mol. Biol.,
January 1, 2008;
38(1):
105 - 113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Slofstra, M. F. Bijlsma, A. P. Groot, P. H. Reitsma, T. Lindhout, H. ten Cate, and C. A. Spek
Protease-activated receptor-4 inhibition protects from multiorgan failure in a murine model of systemic inflammation
Blood,
November 1, 2007;
110(9):
3176 - 3182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Winter, K. Taut, F. Langer, M. Mack, D. E. Briles, J. C. Paton, R. Maus, M. Srivastava, T. Welte, and U. A. Maus
FMS-Like Tyrosine Kinase 3 Ligand Aggravates the Lung Inflammatory Response to Streptococcus pneumoniae Infection in Mice: Role of Dendritic Cells
J. Immunol.,
September 1, 2007;
179(5):
3099 - 3108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Dessing, K. F. van der Sluijs, S. Florquin, S. Akira, and T. van der Poll
Toll-Like Receptor 2 Does Not Contribute to Host Response during Postinfluenza Pneumococcal Pneumonia
Am. J. Respir. Cell Mol. Biol.,
May 1, 2007;
36(5):
609 - 614.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Winter, K. Taut, M. Srivastava, F. Langer, M. Mack, D. E. Briles, J. C. Paton, R. Maus, T. Welte, M. D. Gunn, et al.
Lung-Specific Overexpression of CC Chemokine Ligand (CCL) 2 Enhances the Host Defense to Streptococcus pneumoniae Infection in Mice: Role of the CCL2-CCR2 Axis
J. Immunol.,
May 1, 2007;
178(9):
5828 - 5838.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. A. Maus, M. Backi, C. Winter, M. Srivastava, M. K. Schwarz, T. Ruckle, J. C. Paton, D. Briles, M. Mack, T. Welte, et al.
Importance of Phosphoinositide 3-Kinase {gamma} in the Host Defense against Pneumococcal Infection
Am. J. Respir. Crit. Care Med.,
May 1, 2007;
175(9):
958 - 966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Marks, T. Burns, M. Abadi, B. Seyoum, J. Thornton, E. Tuomanen, and L.-a. Pirofski
Influence of Neutropenia on the Course of Serotype 8 Pneumococcal Pneumonia in Mice
Infect. Immun.,
April 1, 2007;
75(4):
1586 - 1597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zhou and L. Kobzik
Effect of Concentrated Ambient Particles on Macrophage Phagocytosis and Killing of Streptococcus pneumoniae
Am. J. Respir. Cell Mol. Biol.,
April 1, 2007;
36(4):
460 - 465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. McNamee and A. G. Harmsen
Both Influenza-Induced Neutrophil Dysfunction and Neutrophil-Independent Mechanisms Contribute to Increased Susceptibility to a Secondary Streptococcus pneumoniae Infection
Infect. Immun.,
December 1, 2006;
74(12):
6707 - 6721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Marriott, P. G. Hellewell, S. S. Cross, P. G. Ince, M. K. B. Whyte, and D. H. Dockrell
Decreased Alveolar Macrophage Apoptosis Is Associated with Increased Pulmonary Inflammation in a Murine Model of Pneumococcal Pneumonia
J. Immunol.,
November 1, 2006;
177(9):
6480 - 6488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hodge, G. Hodge, S. Brozyna, H. Jersmann, M. Holmes, and P. N. Reynolds
Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages
Eur. Respir. J.,
September 1, 2006;
28(3):
486 - 495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. N. Ballinger, R. Paine III, C. H. C. Serezani, D. M. Aronoff, E. S. Choi, T. J. Standiford, G. B. Toews, and B. B. Moore
Role of Granulocyte Macrophage Colony-Stimulating Factor during Gram-Negative Lung Infection with Pseudomonas aeruginosa
Am. J. Respir. Cell Mol. Biol.,
June 1, 2006;
34(6):
766 - 774.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lee, H. G. Remold, M. H. Ieong, and H. Kornfeld
Macrophage Apoptosis in Response to High Intracellular Burden of Mycobacterium tuberculosis Is Mediated by a Novel Caspase-Independent Pathway
J. Immunol.,
April 1, 2006;
176(7):
4267 - 4274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Knapp, C. W. Wieland, S. Florquin, R. Pantophlet, L. Dijkshoorn, N. Tshimbalanga, S. Akira, and T. van der Poll
Differential Roles of CD14 and Toll-like Receptors 4and 2 in Murine Acinetobacter Pneumonia
Am. J. Respir. Crit. Care Med.,
January 1, 2006;
173(1):
122 - 129.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Tachado, J. Zhang, J. Zhu, N. Patel, and H. Koziel
HIV Impairs TNF-{alpha} Release in Response to Toll-Like Receptor 4 Stimulation in Human Macrophages In Vitro
Am. J. Respir. Cell Mol. Biol.,
December 1, 2005;
33(6):
610 - 621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Renckens, J. J. T. H. Roelofs, S. A. J. ter Horst, C. van 't Veer, S. R. Havik, S. Florquin, G. T. M. Wagenaar, J. C. M. Meijers, and T. van der Poll
Absence of Thrombin-Activatable Fibrinolysis Inhibitor Protects against Sepsis-Induced Liver Injury in Mice
J. Immunol.,
November 15, 2005;
175(10):
6764 - 6771.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Burns, M. Abadi, and L.-a. Pirofski
Modulation of the Lung Inflammatory Response to Serotype 8 Pneumococcal Infection by a Human Immunoglobulin M Monoclonal Antibody to Serotype 8 Capsular Polysaccharide
Infect. Immun.,
August 1, 2005;
73(8):
4530 - 4538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Suzuki, T. Suda, T. Naito, K. Ide, K. Chida, and H. Nakamura
Impaired Toll-like Receptor 9 Expression in Alveolar Macrophages with No Sensitivity to CpG DNA
Am. J. Respir. Crit. Care Med.,
April 1, 2005;
171(7):
707 - 713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. van Westerloo, S. Florquin, A. M. de Boer, J. Daalhuisen, A. F. de Vos, M. J. Bruno, and T. van der Poll
Therapeutic Effects of Troglitazone in Experimental Chronic Pancreatitis in Mice
Am. J. Pathol.,
March 1, 2005;
166(3):
721 - 728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. W. Wieland, S. Knapp, S. Florquin, A. F. de Vos, K. Takeda, S. Akira, D. T. Golenbock, A. Verbon, and T. van der Poll
Non-Mannose-capped Lipoarabinomannan Induces Lung Inflammation via Toll-like Receptor 2
Am. J. Respir. Crit. Care Med.,
December 15, 2004;
170(12):
1367 - 1374.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-Y. Kwon, A. D. Ogunniyi, M.-H. Choi, S.-N. Pyo, D.-K. Rhee, and J. C. Paton
The ClpP Protease of Streptococcus pneumoniae Modulates Virulence Gene Expression and Protects against Fatal Pneumococcal Challenge
Infect. Immun.,
October 1, 2004;
72(10):
5646 - 5653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. F. van der Sluijs, L. J. R. van Elden, M. Nijhuis, R. Schuurman, J. M. Pater, S. Florquin, M. Goldman, H. M. Jansen, R. Lutter, and T. van der Poll
IL-10 Is an Important Mediator of the Enhanced Susceptibility to Pneumococcal Pneumonia after Influenza Infection
J. Immunol.,
June 15, 2004;
172(12):
7603 - 7609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. van Kaam, R. A. Lachmann, E. Herting, A. De Jaegere, F. van Iwaarden, L. A. Noorduyn, J. H. Kok, J. J. Haitsma, and B. Lachmann
Reducing Atelectasis Attenuates Bacterial Growth and Translocation in Experimental Pneumonia
Am. J. Respir. Crit. Care Med.,
May 1, 2004;
169(9):
1046 - 1053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Knapp, C. W. Wieland, C. van 't Veer, O. Takeuchi, S. Akira, S. Florquin, and T. van der Poll
Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense
J. Immunol.,
March 1, 2004;
172(5):
3132 - 3138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tobin
Tuberculosis, Lung Infections, Interstitial Lung Disease, Social Issues and Journalology in AJRCCM 2003
Am. J. Respir. Crit. Care Med.,
January 15, 2004;
169(2):
288 - 300.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Amano, K. Morimoto, M. Senba, H. Wang, Y. Ishida, A. Kumatori, H. Yoshimine, K. Oishi, N. Mukaida, and T. Nagatake
Essential Contribution of Monocyte Chemoattractant Protein-1/C-C Chemokine Ligand-2 to Resolution and Repair Processes in Acute Bacterial Pneumonia
J. Immunol.,
January 1, 2004;
172(1):
398 - 409.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. H. Dockrell, H. M. Marriott, L. R. Prince, V. C. Ridger, P. G. Ince, P. G. Hellewell, and M. K. B. Whyte
Alveolar Macrophage Apoptosis Contributes to Pneumococcal Clearance in a Resolving Model of Pulmonary Infection
J. Immunol.,
November 15, 2003;
171(10):
5380 - 5388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. I. Ojielo, K. Cooke, P. Mancuso, T. J. Standiford, K. M. Olkiewicz, S. Clouthier, L. Corrion, M. N. Ballinger, G. B. Toews, R. Paine III, et al.
Defective Phagocytosis and Clearance of Pseudomonas aeruginosa in the Lung Following Bone Marrow Transplantation
J. Immunol.,
October 15, 2003;
171(8):
4416 - 4424.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Rijneveld, S. Florquin, P. Bresser, M. Levi, V. de Waard, R. Lijnen, J. S. Van der Zee, P. Speelman, P. Carmeliet, and T. van der Poll
Plasminogen activator inhibitor type-1 deficiency does not influence the outcome of murine pneumococcal pneumonia
Blood,
August 1, 2003;
102(3):
934 - 939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Rubins
Alveolar Macrophages: Wielding the Double-Edged Sword of Inflammation
Am. J. Respir. Crit. Care Med.,
January 15, 2003;
167(2):
103 - 104.
[Full Text]
[PDF]
|
|
|
Copyright © 2003 American Thoracic Society
|
|
|
