PMID- 22964851
OWN - NLM
STAT- MEDLINE
DCOM- 20130107
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 92
IP  - 11
DP  - 2012 Nov
TI  - Heme oxygenase-1 promotes granuloma development and protects against 
      dissemination of mycobacteria.
PG  - 1541-52
LID - 10.1038/labinvest.2012.125 [doi]
AB  - Non-tuberculous mycobacterial (NTM) infections occur in both immunocompromised 
      and immunocompetent hosts and are an increasingly recognized cause of morbidity 
      and mortality. The hallmark of pulmonary mycobacterial infections is the 
      formation of granuloma in the lung. Our study focuses on the role of heme 
      oxygenase-1 (HO-1), a cytoprotective enzyme, in the regulation of granuloma 
      development and maturation following infection with Mycobacterium avium. We 
      examined the role of HO-1 in regulating monocyte chemoattractant protein-1 
      (MCP-1) and chemokine receptor 2 (CCR2), two molecules involved in 
      monocyte-macrophage cell trafficking after infection. We showed that RAW 264.7 
      mouse monocytes exposed to M. avium expressed HO-1 and MCP-1. Inhibition of HO by 
      zinc protoporphyrin-IX led to inhibition of MCP-1 and increased expression of 
      CCR2, its cognate receptor. HO-1(-)/(-) mice did not develop organized granuloma in 
      their lungs, had higher lung colony forming unit of M. avium when infected with 
      intratracheal M. avium, and had loose collections of inflammatory cells in the 
      lung parenchyma. Mycobacteria were found only inside defined granulomas but not 
      outside granuloma in the lungs of HO-1(+)/(+) mice. In HO-1(-)/(-) mice, mycobacteria 
      were also found in the liver and spleen and showed increased mortality. 
      Peripheral blood monocytes isolated from GFP(+) mice and given intravenously to 
      HO-1(+)/(+) mice localized into tight granulomas, while in HO-1(-)/(-) mice they remained 
      diffusely scattered in areas of parenchymal inflammation. Higher MCP-1 levels 
      were found in bronchoalveolar lavage fluid of M. avium infected HO-1(-/-) mice 
      and CCR2 expression was higher in HO-1(-)/(-) alveolar macrophages when compared with 
      HO-1(+)/(+) mice. CCR2 expression localized to granuloma in HO-1(+)/(+) mice but not in 
      the HO-1(-)/(-) mice. These findings strongly suggest that HO-1 plays a protective 
      role in the control of M. avium infection.
FAU - Regev, Doron
AU  - Regev D
AD  - Division of Pulmonary, Critical Care and Sleep Medicine, College of Medicine, 
      University of Florida, Gainesville, FL, USA.
FAU - Surolia, Ranu
AU  - Surolia R
FAU - Karki, Suman
AU  - Karki S
FAU - Zolak, Jason
AU  - Zolak J
FAU - Montes-Worboys, Ana
AU  - Montes-Worboys A
FAU - Oliva, Ocatvio
AU  - Oliva O
FAU - Guroji, Purushotum
AU  - Guroji P
FAU - Saini, Vikram
AU  - Saini V
FAU - Steyn, Adrie Jc
AU  - Steyn AJ
FAU - Agarwal, Anupam
AU  - Agarwal A
FAU - Antony, Veena B
AU  - Antony VB
LA  - eng
GR  - R01 AI080349/AI/NIAID NIH HHS/United States
GR  - R01 ES029981/ES/NIEHS NIH HHS/United States
GR  - R21 AA 014796/AA/NIAAA NIH HHS/United States
GR  - R21 AA014796/AA/NIAAA NIH HHS/United States
GR  - R01 AI076389/AI/NIAID NIH HHS/United States
GR  - 1P30 DK079337/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120910
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Membrane Proteins)
RN  - 0 (Protoporphyrins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 15442-64-5 (zinc protoporphyrin)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chemokine CCL2/*metabolism
MH  - Colony Count, Microbial
MH  - Granuloma/*enzymology/microbiology
MH  - Heme Oxygenase-1/*metabolism
MH  - Lung/pathology
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mycobacterium avium
MH  - Protoporphyrins
MH  - RNA, Messenger/metabolism
MH  - Receptors, CCR2/*metabolism
MH  - Tuberculosis, Pulmonary/*enzymology/microbiology/pathology
PMC - PMC4017357
MID - NIHMS560288
EDAT- 2012/09/12 06:00
MHDA- 2013/01/08 06:00
PMCR- 2014/05/12
CRDT- 2012/09/12 06:00
PHST- 2012/09/12 06:00 [entrez]
PHST- 2012/09/12 06:00 [pubmed]
PHST- 2013/01/08 06:00 [medline]
PHST- 2014/05/12 00:00 [pmc-release]
AID - S0023-6837(22)00243-4 [pii]
AID - 10.1038/labinvest.2012.125 [doi]
PST - ppublish
SO  - Lab Invest. 2012 Nov;92(11):1541-52. doi: 10.1038/labinvest.2012.125. Epub 2012 
      Sep 10.