title: Migration of CD11b+ accessory cells during murine lung regeneration.
abstract: In many mammalian species, the removal of one lung leads to growth of the remaining lung to near-baseline levels. In studying post-pneumonectomy mice, we used morphometric measures to demonstrate neoalveolarization within 21 days of pneumonectomy. Of note, the detailed histology during this period demonstrated no significant pulmonary inflammation. To identify occult blood-borne cells, we used a parabiotic model (wild-type/GFP) of post-pneumonectomy lung growth. Flow cytometry of post-pneumonectomy lung digests demonstrated a rapid increase in the number of cells expressing the hematopoietic membrane molecule CD11b; 64.5% of the entire GFP(+) population were CD11b(+). Fluorescence microscopy demonstrated that the CD11b(+) peripheral blood cells migrated into both the interstitial tissue and alveolar airspace compartments. Pneumonectomy in mice deficient in CD11b (CD18(-/-) mutants) demonstrated near-absent leukocyte migration into the airspace compartment (p<.001) and impaired lung growth as demonstrated by lung weight (p<.05) and lung volume (p<.05). Transcriptional activity of the partitioned CD11b(+) cells demonstrated significantly increased transcription of Angpt1, Il1b, and Mmp8, Mmp9, Ncam1, Sele, Sell, Selp in the alveolar airspace and Adamts2, Ecm1, Egf, Mmp7, Npr1, Tgfb2 in the interstitial tissue (>4-fold regulation; p<.05). These data suggest that blood-borne CD11b(+) cells represent a population of accessory cells contributing to post-pneumonectomy lung growth.
authors: Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Kenji
authors: K
authors: Chamoto
authors: Barry C
authors: BC
authors: Gibney
authors: Grace S
authors: GS
authors: Lee
authors: Maximilian
authors: M
authors: Ackermann
authors: Moritz A
authors: MA
authors: Konerding
authors: Akira
authors: A
authors: Tsuda
authors: Steven J
authors: SJ
authors: Mentzer
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism*; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D007962:Leukocytes / Q000166:cytology / Q000502:physiology; D008168:Lung / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011013:Pneumonectomy; D012038:Regeneration; D059467:Transcriptome
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens
references: Angiogenesis. 2012 Mar;15(1):23-32
references: 21969134
references: Am J Respir Cell Mol Biol. 2007 Apr;36(4):435-41
references: 17122367
references: Am J Respir Cell Mol Biol. 2012 Mar;46(3):283-9
references: 21921238
references: Eur Respir J. 2008 Mar;31(3):515-22
references: 18032439
references: J Cell Physiol. 2012 Feb;227(2):821-8
references: 21503883
references: Cancer Res. 1996 Oct 15;56(20):4625-9
references: 8840975
references: Blood. 2009 May 21;113(21):5266-76
references: 19147786
references: Curr Opin Genet Dev. 2006 Oct;16(5):463-8
references: 16919446
references: Clin Exp Immunol. 1999 Feb;115(2):315-23
references: 9933459
references: Exp Lung Res. 2011 Jun;37(5):301-9
references: 21574875
references: N Engl J Med. 2011 May 12;364(19):1795-806
references: 21561345
references: Respir Physiol. 1974 Mar;20(2):105-15
references: 4826745
references: Cancer Cell. 2005 Sep;8(3):211-26
references: 16169466
references: J Exp Med. 1997 Oct 20;186(8):1357-64
references: 9334375
references: Eur J Immunol. 1979 Apr;9(4):301-6
references: 89034
references: Am J Physiol Lung Cell Mol Physiol. 2003 Jan;284(1):L242-5
references: 12388332
references: Blood. 2010 May 27;115(21):4302-12
references: 20110420
references: N Engl J Med. 2012 Jul 19;367(3):244-7
references: 22808959
references: Tissue Eng Part A. 2010 Aug;16(8):2457-66
references: 20218762
references: Nature. 2006 Jun 29;441(7097):1075-9
references: 16810242
references: J Immunol. 2003 Sep 15;171(6):3128-35
references: 12960339
references: Nature. 2005 Sep 15;437(7057):417-21
references: 16163358
references: Physiol Rev. 1999 Jan;79(1):181-213
references: 9922371
references: J Cell Physiol. 2012 Sep;227(9):3208-15
references: 22105735
references: Mol Aspects Med. 2011 Apr;32(2):123-45
references: 21565215
references: Clin Immunol Immunopathol. 1993 Jun;67(3 Pt 2):S16-24
references: 8500276
references: Nat Med. 2003 Jun;9(6):789-95
references: 12740570
references: Blood. 1999 Nov 15;94(10):3281-8
references: 10552936
references: Circ Res. 2000 Sep 1;87(5):378-84
references: 10969035
references: Respir Res. 2011 Jul 27;12:98
references: 21794125
references: Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12947-52
references: 8917524
references: Blood. 2010 Aug 5;116(5):829-40
references: 20404134
references: Exp Lung Res. 2012 Oct;38(8):396-405
references: 22905715
references: Am J Respir Crit Care Med. 2004 Aug 1;170(3):319-43
references: 15280177
references: Nature. 1952 Jul 19;170(4316):116-7
references: 14957040
references: BMC Mol Biol. 2006 Jan 31;7:3
references: 16448564