Role of alveolar macrophages in the regulation of local and systemic inflammation after lung contusion.
BACKGROUND
Blunt chest trauma is an injury that enhances the morbidity and mortality rate, particularly in the context of polytrauma. Our previous studies showed local and systemic inflammatory alterations after blunt chest trauma in mice. This study was designed to determine whether alveolar macrophages (AMΦ) have an alleviative role in this posttraumatic inflammation.


METHODS
AMΦ of male C3H/HeN mice were depleted by instillation of clodronate liposomes into the lung before blunt chest trauma induced by a single blast wave. In bronchoalveolar lavage, lung homogenates, plasma, and cell culture supernatants of Kupffer cells, peripheral blood mononuclear cells, splenic macrophages, and splenocytes isolated 2 hours or 24 hours after chest trauma mediator concentrations were determined by multiplex assay or enzyme-linked immunosorbent assay.


RESULTS
In bronchoalveolar lavage, AMΦ depletion led to increased monocyte chemoattractant protein 1 and regulated and normal T cell expressed and secreted (RANTES) concentrations as well as an attenuated increase of interleukin 6 concentrations after chest trauma. Bronchoalveolar lavage keratinocyte-derived chemokine concentrations increased in nontraumatized but AMΦ-depleted animals with no further change after chest trauma. Cytokine concentrations in lung homogenates were altered in the same way as in bronchoalveolar lavage early after trauma. In the plasma of AMΦ-depleted animals, interleukin 6 concentrations were slightly decreased after chest trauma. Depletion of AMΦ abrogated the trauma-induced decrease of Kupffer cell chemokine release. Cytokine concentrations of blood monocytes, splenic macrophages, and splenocyte supernatants were not influenced by AMΦ depletion.


CONCLUSIONS
These depletion experiments show that AMΦ ameliorate the inflammatory response after blunt chest trauma. Taken together, this study gives relevant insights into the regulative role of AMΦ during the local and systemic inflammation after lung contusion.
From the Departments of Trauma Surgery, Hand, Plastic and Reconstructive Surgery (U.N., A.P., J.S.F., S.T.B., F.G., M.W.K., D.H.S.) and Clinical Chemistry (S.Z.), University of Ulm, Ulm, Germany.
Ulrike
U
Niesler
Annette
A
Palmer
Janine S
JS
Fröba
Sonja T
ST
Braumüller
Shaoxia
S
Zhou
Florian
F
Gebhard
Markus W
MW
Knöferl
Daniel H
DH
Seitz
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002465:Cell Movement; D018946:Chemokine CCL5 / Q000032:analysis / Q000378:metabolism; D018925:Chemokines / Q000097:blood / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology; D003288:Contusions / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018836:Inflammation Mediators / Q000097:blood* / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D055370:Lung Injury / Q000378:metabolism* / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011897:Random Allocation; D012016:Reference Values; D012380:Role; D012680:Sensitivity and Specificity; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism / Q000503:physiopathology*; D014949:Wounds, Nonpenetrating / Q000378:metabolism* / Q000503:physiopathology
D018946:Chemokine CCL5; D018925:Chemokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D004002:Clodronic Acid; C074302:keratinocyte-derived chemokines