Selective depletion of alveolar macrophages in polymicrobial sepsis increases lung injury, bacterial load and mortality but does not affect cytokine release.
BACKGROUND
Resident tissue macrophages exert important functions during severe systemic infection and contribute to changes in local as well as systemic immune responses. Alveolar macrophages (AM) play a crucial role in airway diseases and in the defense against microorganisms invading the body via the bronchopulmonary tract. It has been postulated that AM are involved in the development of acute local disorders as a consequence of extrapulmonary stimuli like pancreatitis, peritonitis, or trauma.


OBJECTIVE
The aim of this study was to analyze the local and systemic role of AM during sepsis using selective AM depletion in the murine colon ascendens stent peritonitis (CASP) model of polymicrobial sepsis.


METHODS
48 h prior to CASP surgery, AM of female C57BL/6 mice were selectively depleted by intratracheal application of clodronate liposomes (Lipo-clod). For control purposes, phosphate-buffered saline (PBS) liposomes (Lipo-PBS) were used.


RESULTS
CASP led to significantly elevated levels of local and systemic cytokines independent of the presence of AM. In contrast, levels of gut-derived bacteria in bronchoalveolar lavage and lung of septic mice were significantly higher in Lipo-clod-treated animals compared to Lipo-PBS-treated animals. After CASP-induced sepsis, local barrier dysfunction in the lung was detected; AM depletion resulted in severely enhanced development of acute lung injury. Consequently, Lipo-clod-treated animals showed strongly reduced survival rates after CASP.


CONCLUSIONS
Contrarily to other macrophage populations, AM do not significantly contribute to local and systemic cytokine release during polymicrobial abdominal sepsis. AM have important protective functions for local clearance of gut-derived bacteria and attenuation of lung injury.
Traeger
Tobias
T
Department of Surgery, University of Greifswald, Greifswald, Germany. Traeger@uni-greifswald.de
Kessler
Wolfram
W
Hilpert
Anne
A
Mikulcak
Marlene
M
Entleutner
Markus
M
Koerner
Pia
P
Westerholt
Alexandra
A
Cziupka
Katharina
K
van Rooijen
Nico
N
Heidecke
Claus-Dieter
CD
Maier
Stefan
S
D055371:Acute Lung Injury / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004801:Eosine Yellowish-(YS); D005260:Female; D006416:Hematoxylin; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016019:Survival Analysis
D016207:Cytokines; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin