PMID- 19218354
OWN - NLM
STAT- MEDLINE
DCOM- 20090617
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 296
IP  - 5
DP  - 2009 May
TI  - Maternal exposure to endotoxin delays alveolarization during postnatal rat lung 
      development.
PG  - L726-37
LID - 10.1152/ajplung.90405.2008 [doi]
AB  - Maternal bacterial infections adversely affect lung development by crossing the 
      placental barrier and infecting the developing fetus. The underlying mechanism 
      negatively affecting pulmonary development remains unknown. Herein, we 
      investigated whether a systemic maternal infection affects postnatal inflammation 
      and alveolar development. Pregnant rats were injected with 2.5 mg/kg LPS on day 
      20 and 21 (term = 22 days). Postnatal (PN0-21) mRNA and protein expression of 
      cytokines (IL-1beta, IL-6, IL-10, CXCL1/2, TNFalpha) and genes implicated in 
      alveologenesis [tropoelastin, lysyl oxidase (LOX), lysyl oxidase-like (LOXL)1, 
      tenascin-C (TNC), fibulin 5, vascular endothelial growth factor (VEGF-A), VEGF 
      receptor (VEGFR)2, VEGFR1, platelet-derived growth factor (PDGF)A, PDGFB, and 
      PDGFRalpha] were quantified by real-time PCR and beadlyte technology. Lung 
      transcript and protein levels of IL-1beta, IL-6, and CXCL1/2 were significantly 
      greater in LPS-exposed pups than those of control pups at PN0, 2, 6, 10, and 14. 
      Bronchoalveolar lavage fluid (BALF) of LPS-exposed animals contained 
      significantly more macrophages at PN2 and 14 than BALF of control pups. 
      Morphometric analysis revealed that LPS-exposed animals had fewer and larger 
      alveoli, fewer secondary septa, and decreased peripheral vessel density when 
      compared with control pups. This morphological delay in alveolar development 
      disappeared after PN14. Tropoelastin, LOXL1, VEGF, VEGFR2, and PDGFRalpha mRNA 
      expression of LPS-exposed animals was significantly greater than those of control 
      animals in PN2-14 lungs. TNC, LOX, fibulin 5, VEGFR1, PDGFA, and PDGFB expression 
      was not affected by maternal LPS exposure. Together, the data demonstrate that 
      maternal exposure to endotoxin results in a prolonged pulmonary inflammation 
      postnatally, altered gene expression of molecules implicated in alveologenesis, 
      and delayed morphological maturation of the lung.
FAU - Cao, Lei
AU  - Cao L
AD  - The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
FAU - Wang, Jinxia
AU  - Wang J
FAU - Tseu, Irene
AU  - Tseu I
FAU - Luo, Daochun
AU  - Luo D
FAU - Post, Martin
AU  - Post M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090213
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Chemokines)
RN  - 0 (Endotoxins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tropoelastin)
RN  - EC 1.4.3.13 (Protein-Lysine 6-Oxidase)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Body Weight/drug effects
MH  - Bronchoalveolar Lavage Fluid/cytology
MH  - Chemokines/genetics/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endotoxins/*administration & dosage/*pharmacology
MH  - Female
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Inflammation/pathology
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Lipopolysaccharides/administration & dosage/pharmacology
MH  - Organ Size/drug effects
MH  - Organogenesis/*drug effects
MH  - Placenta/drug effects/metabolism
MH  - Placentation
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*pathology
MH  - Protein-Lysine 6-Oxidase/genetics/metabolism
MH  - Pulmonary Alveoli/*embryology/growth & development/metabolism/pathology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Tropoelastin/genetics/metabolism
EDAT- 2009/02/17 09:00
MHDA- 2009/06/18 09:00
CRDT- 2009/02/17 09:00
PHST- 2009/02/17 09:00 [entrez]
PHST- 2009/02/17 09:00 [pubmed]
PHST- 2009/06/18 09:00 [medline]
AID - 90405.2008 [pii]
AID - 10.1152/ajplung.90405.2008 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2009 May;296(5):L726-37. doi: 
      10.1152/ajplung.90405.2008. Epub 2009 Feb 13.