PMID- 19617401
OWN - NLM
STAT- MEDLINE
DCOM- 20100610
LR  - 20211020
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 42
IP  - 6
DP  - 2010 Jun
TI  - MCP-1 antibody treatment enhances damage and impedes repair of the alveolar 
      epithelium in influenza pneumonitis.
PG  - 732-43
LID - 10.1165/rcmb.2008-0423OC [doi]
AB  - Recent studies have demonstrated an essential role of alveolar macrophages during 
      influenza virus infection. Enhanced mortalities were observed in 
      macrophage-depleted mice and pigs after influenza virus infection, but the basis 
      for the enhanced pathogenesis is unclear. This study revealed that blocking 
      macrophage recruitment into the lungs in a mouse model of influenza pneumonitis 
      resulted in enhanced alveolar epithelial damage and apoptosis, as evaluated by 
      histopathology, immunohistochemistry, Western blot, RT-PCR, and TUNEL assays. 
      Abrogation of macrophage recruitment was achieved by treatment with monoclonal 
      antibody against monocyte chemoattractant protein-1 (MCP-1) after sub-lethal 
      challenge with mouse-adapted human influenza A/Aichi/2/68 virus. Interestingly, 
      elevated levels of hepatocyte growth factor (HGF), a mitogen for alveolar 
      epithelium, were detected in bronchoalveolar lavage samples and in lung 
      homogenates of control untreated and nonimmune immunoglobulin (Ig)G-treated mice 
      after infection compared with anti-MCP-1-treated infected mice. The lungs of 
      control animals also displayed strongly positive HGF staining in alveolar 
      macrophages as well as alveolar epithelial cell hyperplasia. Co-culture of 
      influenza virus-infected alveolar epithelial cells with freshly isolated alveolar 
      macrophages induced HGF production and phagocytic activity of macrophages. 
      Recombinant HGF added to mouse lung explants after influenza virus infection 
      resulted in enhanced BrdU labeling of alveolar type II epithelial cells, 
      indicating their proliferation, in contrast with anti-HGF treatment showing 
      significantly reduced epithelial regeneration. Our data indicate that inhibition 
      of macrophage recruitment augmented alveolar epithelial damage and apoptosis 
      during influenza pneumonitis, and that HGF produced by macrophages in response to 
      influenza participates in the resolution of alveolar epithelium.
FAU - Narasaraju, T
AU  - Narasaraju T
AD  - Infectious Diseases Program, Department of Microbiology, Yong Loo Lin School of 
      Medicine, National University of Singapore, 5 Science Drive 2, Kent Ridge 117597, 
      Singapore. micctk@nus.edu.sg
FAU - Ng, H H
AU  - Ng HH
FAU - Phoon, M C
AU  - Phoon MC
FAU - Chow, Vincent T K
AU  - Chow VT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090717
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Cxcl1 protein, mouse)
RN  - 0 (Recombinant Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage
MH  - Apoptosis
MH  - Blotting, Western
MH  - Body Weight
MH  - Bronchoalveolar Lavage Fluid/immunology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Chemokine CCL2/*immunology
MH  - Chemokine CXCL1/blood
MH  - Chemotaxis, Leukocyte
MH  - Coculture Techniques
MH  - Disease Models, Animal
MH  - Female
MH  - Hepatocyte Growth Factor/metabolism
MH  - Humans
MH  - Hyperplasia
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Influenza A virus/*pathogenicity
MH  - Injections, Intraperitoneal
MH  - Macrophages, Alveolar/*immunology/metabolism/pathology/virology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Orthomyxoviridae Infections/*immunology/metabolism/pathology/virology
MH  - Peroxidase/metabolism
MH  - Pneumonia, Viral/*immunology/metabolism/pathology/virology
MH  - Pulmonary Alveoli/*immunology/metabolism/pathology/virology
MH  - Recombinant Proteins/metabolism
MH  - Respiratory Mucosa/*immunology/metabolism/pathology/virology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Viral Load
PMC - PMC2891499
EDAT- 2009/07/21 09:00
MHDA- 2010/06/11 06:00
PMCR- 2010/12/01
CRDT- 2009/07/21 09:00
PHST- 2009/07/21 09:00 [entrez]
PHST- 2009/07/21 09:00 [pubmed]
PHST- 2010/06/11 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - 2008-0423OC [pii]
AID - ajrccm426732 [pii]
AID - 10.1165/rcmb.2008-0423OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2010 Jun;42(6):732-43. doi: 10.1165/rcmb.2008-0423OC. 
      Epub 2009 Jul 17.