PMID- 14615370
OWN - NLM
STAT- MEDLINE
DCOM- 20040415
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 6
DP  - 2004 Mar 15
TI  - A critical role for CCR2/MCP-1 interactions in the development of idiopathic 
      pneumonia syndrome after allogeneic bone marrow transplantation.
PG  - 2417-26
AB  - Idiopathic pneumonia syndrome (IPS) is a major complication after allogeneic bone 
      marrow transplantation (allo-BMT) and involves the infiltration of donor 
      leukocytes and the secretion of inflammatory cytokines. We hypothesized that 
      leukocyte recruitment during IPS is dependent in part upon interactions between 
      chemokine receptor 2 (CCR2) and its primary ligand monocyte chemoattractant 
      protein-1 (MCP-1). To test this hypothesis, IPS was induced in a lethally 
      irradiated parent --> F1 mouse BMT model. Compared with syngeneic controls, 
      pulmonary expression of MCP-1 and CCR2 mRNA was significantly increased after 
      allo-BMT. Transplantation of CCR2-deficient (CCR2-/-) donor cells resulted in a 
      significant reduction in IPS severity compared with transplantation of wild-type 
      (CCR2+/+) cells and in reduced bronchoalveolar lavage (BAL) fluid cellularity and 
      BAL fluid levels of tumor necrosis factor-alpha (TNF-alpha) and soluble p55 TNF 
      receptor (sTNFRI). In addition, neutralization of MCP-1 resulted in significantly 
      decreased lung injury compared with control-treated allogeneic recipients. 
      Experimental data correlated with preliminary clinical findings; patients with 
      IPS have elevated levels of MCP-1 in the BAL fluid at the time of diagnosis. 
      Collectively, these data demonstrate that CCR2/MCP-1 interactions significantly 
      contribute to the development of experimental IPS and suggest that interventions 
      blocking these receptor-ligand interactions may represent novel strategies to 
      prevent or treat this lethal complication after allo-BMT.
FAU - Hildebrandt, Gerhard C
AU  - Hildebrandt GC
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, 48109, USA.
FAU - Duffner, Ulrich A
AU  - Duffner UA
FAU - Olkiewicz, Krystyna M
AU  - Olkiewicz KM
FAU - Corrion, Leigh A
AU  - Corrion LA
FAU - Willmarth, Nicole E
AU  - Willmarth NE
FAU - Williams, Debra L
AU  - Williams DL
FAU - Clouthier, Shawn G
AU  - Clouthier SG
FAU - Hogaboam, Cory M
AU  - Hogaboam CM
FAU - Reddy, Pavan R
AU  - Reddy PR
FAU - Moore, Bethany B
AU  - Moore BB
FAU - Kuziel, William A
AU  - Kuziel WA
FAU - Liu, Chen
AU  - Liu C
FAU - Yanik, Gregory
AU  - Yanik G
FAU - Cooke, Kenneth R
AU  - Cooke KR
LA  - eng
GR  - 5K12HD028820-12/HD/NICHD NIH HHS/United States
GR  - R01-HL072258-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031113
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/*adverse effects
MH  - Bronchoalveolar Lavage Fluid/cytology/immunology
MH  - Chemokine CCL2/*metabolism
MH  - Cytokines/metabolism
MH  - Female
MH  - Lung/immunology/pathology
MH  - Macrophages/immunology/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Monocytes/immunology/pathology
MH  - Pneumonia/*immunology/*metabolism/pathology
MH  - RNA, Messenger/metabolism
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/*metabolism
MH  - Severity of Illness Index
MH  - T-Lymphocytes/immunology/pathology
MH  - Transplantation, Homologous
EDAT- 2003/11/15 05:00
MHDA- 2004/04/16 05:00
CRDT- 2003/11/15 05:00
PHST- 2003/11/15 05:00 [pubmed]
PHST- 2004/04/16 05:00 [medline]
PHST- 2003/11/15 05:00 [entrez]
AID - S0006-4971(20)50045-1 [pii]
AID - 10.1182/blood-2003-08-2708 [doi]
PST - ppublish
SO  - Blood. 2004 Mar 15;103(6):2417-26. doi: 10.1182/blood-2003-08-2708. Epub 2003 Nov 
      13.