Organizing pneumonia in mice and men.
Organizing pneumonia is a reaction pattern and an inflammatory response to acute lung injuries, and is characterized by intraluminal plugs of granulation tissue in distal airspaces. In contrast to other fibrotic pulmonary diseases, organizing pneumonia is generally responsive to corticosteroids. However, some patients do not respond to treatment, leading to respiratory failure and potentially death (up to 15 % of patients). In order to devise new therapeutic strategies, a better understanding of the disease's pathomechanisms is warranted. We previously generated a mouse model overexpressing CCL2, which generates organizing pneumonia-like changes, morphologically comparable to human patients. In this study, we investigated whether the histopathological similarities of human and murine pulmonary organizing pneumonia lesions also involve similar molecular pathways.



We analyzed the similarities and differences of fibrosis-associated gene expression in individual compartments from patients with organizing pneumonia and transgenic (CCL2) mice using laser-assisted microdissection, real-time PCR and immunohistochemistry.



Gene expression profiling of human and murine organizing pneumonia lesions showed in part comparable expression levels of pivotal genes, notably of TGFB1/Tgfb1, TIMP1/Timp1, TIMP2/Timp2, COL3A1/Col3a1, CXCL12/Cxcl12, MMP2/Mmp2 and IL6/Il6. Hence, the transgenic CCL2 mouse model shows not only pathogenomic and morphological features of human organizing pneumonia but also a similar inflammatory profile.



We suggest that the CCL2-overexpressing transgenic mouse model (CCL2 Tg mice) is suitable for further investigation of fibrotic pulmonary remodeling, particularly of organizing pneumonia pathogenesis and for the search for novel therapeutic strategies.
Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany. Izykowski.Nicole@mh-hannover.de.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany. Izykowski.Nicole@mh-hannover.de.|German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Bad Nauheim, Germany. Izykowski.Nicole@mh-hannover.de.
Nicole
N
Izykowski
Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.|German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Bad Nauheim, Germany.
Mark
M
Kuehnel
Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Kais
K
Hussein
Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Kristin
K
Mitschke
Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Michael
M
Gunn
Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.|German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Bad Nauheim, Germany.
Sabina
S
Janciauskiene
Department of Thoracic Surgery, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.|German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Bad Nauheim, Germany.
Axel
A
Haverich
Department of Thoracic Surgery, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.|German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Bad Nauheim, Germany.
Gregor
G
Warnecke
Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.|German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Bad Nauheim, Germany.
Florian
F
Laenger
Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.|German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Bad Nauheim, Germany.
Ulrich
U
Maus
Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.|German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Bad Nauheim, Germany.
Danny
D
Jonigk
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008822:Mice, Transgenic; D011014:Pneumonia / Q000150:complications / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D018932:Chemokine CCL2; D012333:RNA, Messenger
CCL2 transgenic mouse; Laser-assisted microdissection; Organizing pneumonia