PMID- 8918364
OWN - NLM
STAT- MEDLINE
DCOM- 19961218
LR  - 20131121
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 15
IP  - 5
DP  - 1996 Nov
TI  - Intratracheal administration of hepatocyte growth factor/scatter factor 
      stimulates rat alveolar type II cell proliferation in vivo.
PG  - 574-81
AB  - Alveolar epithelial injury occurs universally in common respiratory illnesses 
      associated with diffuse lung damage. After alveolar injury, type II cells 
      proliferate and reestablish epithelial integrity, thereby restoring normal lung 
      structure and function. However, the regulation of type II cell proliferation and 
      alveolar epithelial repair is poorly understood. Hepatocyte growth factor/scatter 
      factor (HGF/SF) is a heparin-binding growth factor that has been shown to be 
      mitogenic for cultured alveolar type II cells. In this study, we determined the 
      effect of intratracheal instillation of rhHGF/SF on type II cell proliferation in 
      vivo. To quantify the alveolar type II cell proliferative response, we developed 
      a double-label immunohistochemical technique to detect replicating alveolar type 
      II cells in formalin-fixed lung sections that utilized the identification of 
      proliferating cells by bromodeoxyuridine (BrdUrd) incorporation into DNA and 
      alveolar type II cells by 3F9 immunoreactivity. BrdUrd detection was optimized by 
      enzymatic antigen recovery and silver intensification of the horseradish 
      peroxidase reaction product. Intratracheal instillation of rhHGF/SF induced a 
      time- and dose-dependent increase in type II cell proliferation. The type II cell 
      labeling index increased to 12.3 +/- 6.0% 48 h after 1.0 mg/kg rhHGF/SF 
      administration, compared with 2.6 +/- 0.9% after PBS instillation. To compare the 
      normal type II cell reparative response with the level of proliferation after 
      exogenous rhHGF/SF administration, we measured the specific alveolar type II cell 
      labeling index in rat lung sections obtained from animals exposed to hyperoxia 
      for 50 h and then allowed to recover in room air. After 1 day of recovery, the 
      alveolar type II cell labeling index was 0.45 +/- 0.2%. The specific labeling 
      index increased to 5.4 +/- 1.3% at 2 days and then declined to 0.31 +/- 0.16% 5 
      days after hyperoxia exposure. In animals not exposed to hyperoxia, the alveolar 
      type II cell labeling index was 0.6 +/- 0.14%. These studies demonstrated that 
      intratracheal instillation of rhHGF/SF promoted alveolar type II cell 
      proliferation in vivo. The maximal level of type II cell proliferation after 
      rhHGF/SF administration was more than twice that reached during recovery from 
      hyperoxia exposure. Thus, intratracheal instillation of HGF/SF may provide a 
      potential strategy to promote type II cell proliferation and augment alveolar 
      epithelial repair after lung injury.
FAU - Panos, R J
AU  - Panos RJ
AD  - Pulmonary Division, Northwestern University Medical School, Chicago, Illinois 
      60611, USA.
FAU - Patel, R
AU  - Patel R
FAU - Bak, P M
AU  - Bak PM
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Antigens)
RN  - 0 (Lectins)
RN  - 0 (Plant Lectins)
RN  - 27KFF3PMTU (maclurin)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9007-49-2 (DNA)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Animals
MH  - Antigens/analysis
MH  - Bromodeoxyuridine/analysis
MH  - Cell Division/drug effects
MH  - DNA/biosynthesis
MH  - Hepatocyte Growth Factor/*administration & dosage
MH  - Hyperoxia
MH  - *Immunoenzyme Techniques
MH  - Instillation, Drug
MH  - Lectins
MH  - Male
MH  - *Plant Lectins
MH  - Pulmonary Alveoli/chemistry/cytology/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Trachea
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
AID - 10.1165/ajrcmb.15.5.8918364 [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 1996 Nov;15(5):574-81. doi: 
      10.1165/ajrcmb.15.5.8918364.