Altered postnatal lung development in C3H/HeJ mice.
C3H/HeJ mice develop an increase in terminal air space area detectable by postnatal d 14 that persists into adulthood compared with strain-matched controls (C3H/SnJ, C3H/OuJ). Morphometric quantification revealed a 50% increase in terminal air space area by postnatal d 14 and a 2.3-fold increase by 2 mo of age in C3H/HeJ mice. Bacteriologic cultures obtained from the left lung on postnatal d 7 revealed > 100 colony-forming units (CFU)/left lung of predominantly Gram-negative bacteria (GNB) (Escherichia coli and Proteus mirabilis) in 13 of the 14 C3H/HeJ mice compared with 0 of 12 controls demonstrating colonization of the developing lung in C3H/HeJ mice. An approximately threefold increase in macrophages from bronchoalveolar lavage, threefold increases in matrix metalloproteinase 12 (MMP-12) mRNA and protein levels and elevated levels of proinflammatory cytokines monocyte chemoattractant protein (MCP-1) and keratinocyte-derived cytokine (KC) were also found. P. mirabilis obtained from lung cultures in C3H/HeJ mice induced nuclear factor-kappaB (NF-kappaB) activation in human embryonic kidney 293 (HEK 293) cells transfected with TLR5. In C3H/HeJ mice lacking TLR4 signaling, bacterial colonization is associated with chronic inflammation and permanent changes in lung morphology.
Sampath
Venkatesh
V
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Davis
Katy
K
Senft
Albert P
AP
Richardson
Theresa R
TR
Kitzmiller
Joseph A
JA
Berclaz
Pierre Yves
PY
Korfhagen
Thomas R
TR
D000818:Animals; D018893:Bronchoalveolar Lavage; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000254:growth & development* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008171:Lung Diseases / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008176:Lung Volume Measurements; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D053508:Matrix Metalloproteinase 12 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011513:Proteus mirabilis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D016328:NF-kappa B; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; C074302:keratinocyte-derived chemokines; D053508:Matrix Metalloproteinase 12