PMID- 34231378
OWN - NLM
STAT- MEDLINE
DCOM- 20210921
LR  - 20220902
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 321
IP  - 3
DP  - 2021 Sep 1
TI  - M2 macrophages have unique transcriptomes but conditioned media does not promote 
      profibrotic responses in lung fibroblasts or alveolar epithelial cells in vitro.
PG  - L518-L532
LID - 10.1152/ajplung.00107.2021 [doi]
AB  - Macrophages are critical regulators of pulmonary fibrosis. Their plasticity, 
      proximity, and ability to cross talk with structural cells of the lung make them 
      a key cell type of interest in the regulation of lung fibrosis. Macrophages can 
      express a variety of phenotypes, which have been historically represented through 
      an "M1-like" to "M2-like" delineation. In this classification, M1-like 
      macrophages are proinflammatory and have increased phagocytic capacity compared 
      with alternatively activated M2-like macrophages that are profibrotic and are 
      associated with wound healing. Extensive evidence in the field in both patients 
      and animal models aligns pulmonary fibrosis with M2 macrophages. In this study, 
      we performed RNA sequencing (RNAseq) to fully characterize M1- vs. M2-skewed bone 
      marrow-derived macrophages (BMDMs) and investigated the profibrotic abilities of 
      M2 BMDM conditioned media (CM) to promote fibroblast migration and proliferation, 
      alveolar epithelial cell (AEC) apoptosis, and mRNA expression of key fibrotic 
      genes in both fibroblasts and AECs. Although M2 CM-treated fibroblasts had 
      increased migration and M2 CM-treated fibroblasts and AECs had increased 
      expression of profibrotic proteins over M1 CM-treated cells, all differences can 
      be attributed to M2 polarization reagents IL-4 and IL-13 also present in the CM. 
      Collectively, these data suggest that the profibrotic effects associated with M2 
      macrophage CM in vitro are attributable to effects of polarization cytokines 
      rather than additional factors secreted in response to those polarizing 
      cytokines.
FAU - Hult, Elissa M
AU  - Hult EM
AUID- ORCID: 0000-0002-6644-7134
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, Michigan.
FAU - Gurczynski, Stephen J
AU  - Gurczynski SJ
AUID- ORCID: 0000-0002-4238-030X
AD  - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
      Michigan.
FAU - Moore, Bethany B
AU  - Moore BB
AUID- ORCID: 0000-0003-3051-745X
AD  - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
      Michigan.
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
LA  - eng
SI  - figshare/10.6084/m9.figshare.14818566
SI  - figshare/10.6084/m9.figshare.14818545
GR  - F31 HL149150/HL/NHLBI NIH HHS/United States
GR  - R35 HL144481/HL/NHLBI NIH HHS/United States
GR  - T32 AI007413/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210707
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 (Culture Media, Conditioned)
SB  - IM
MH  - Alveolar Epithelial Cells/*metabolism/pathology
MH  - Animals
MH  - Coculture Techniques
MH  - Culture Media, Conditioned/pharmacology
MH  - Female
MH  - Fibroblasts/*metabolism/pathology
MH  - *Gene Expression Regulation
MH  - Macrophages/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Pulmonary Fibrosis/genetics/*metabolism/pathology
MH  - *RNA-Seq
PMC - PMC8461801
OTO - NOTNLM
OT  - M1/M2 macrophage
OT  - RNAseq
OT  - alveolar epithelial cell
OT  - fibroblast
OT  - fibrosis
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2021/07/08 06:00
MHDA- 2021/09/22 06:00
PMCR- 2022/09/01
CRDT- 2021/07/07 08:41
PHST- 2021/07/08 06:00 [pubmed]
PHST- 2021/09/22 06:00 [medline]
PHST- 2021/07/07 08:41 [entrez]
PHST- 2022/09/01 00:00 [pmc-release]
AID - L-00107-2021 [pii]
AID - 10.1152/ajplung.00107.2021 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2021 Sep 1;321(3):L518-L532. doi: 
      10.1152/ajplung.00107.2021. Epub 2021 Jul 7.