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
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