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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Respir+Cell+Mol+Biol
2014 ; 51
(6
): 810-21
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Role of C-C motif ligand 2 and C-C motif receptor 2 in murine pulmonary
graft-versus-host disease after lipopolysaccharide inhalations
#MMPMID24921973
Martinu T
; Gowdy KM
; Nugent JL
; Sun J
; Kinnier CV
; Nelson ME
; Lyes MA
; Kelly FL
; Foster WM
; Gunn MD
; Palmer SM
Am J Respir Cell Mol Biol
2014[Dec]; 51
(6
): 810-21
PMID24921973
show ga
Environmental exposures are a potential trigger of chronic pulmonary
graft-versus-host disease (pGVHD) after successful recovery from hematopoietic
cell transplant (HCT). We hypothesized that inhalations of LPS, a prototypic
environmental stimulus, trigger pGVHD via increased pulmonary recruitment of
donor-derived antigen-presenting cells (APCs) through the C-C motif ligand 2
(CCL2)-C-C motif receptor 2 (CCR2) chemokine axis. B10.BR(H2(k)) and
C57BL/6(H2(b)) mice underwent allogeneic (Allo) or syngeneic (Syn) HCT with
wild-type (WT) C57BL/6, CCL2(-/-), or CCR2(-/-) donors. After 4 weeks, recipient
mice received daily inhaled LPS for 5 days and were killed at multiple time
points. Allo mice exposed to repeated inhaled LPS developed prominent lymphocytic
bronchiolitis, similar to human pGVHD. The increase in pulmonary T cells in Allo
mice after LPS exposures was accompanied by increased CCL2, CCR2, and Type-1
T-helper cytokines as well as by monocytes and monocyte-derived dendritic cells
(moDCs) compared with Syn and nontransplanted controls. Using CCL2(-/-) donors
leads to a significant decrease in lung DCs but to only mildly reduced CD4 T
cells. Using CCR2(-/-) donors significantly reduces lung DCs and moDCs but does
not change T cells. CCL2 or CCR2 deficiency does not alter pGVHD pathology but
increases airway hyperreactivity and IL-5 or IL-13 cytokines. Our results show
that hematopoietic donor-derived CCL2 and CCR2 regulate recruitment of APCs to
the Allo lung after LPS exposure. Although they do not alter pathologic pGVHD,
their absence is associated with increased airway hyperreactivity and IL-5 and
IL-13 cytokines. These results suggest that the APC changes that result from
CCL2-CCR2 blockade may have unexpected effects on T cell differentiation and
physiologic outcomes in HCT.
|Animals
[MESH]
|Cell Differentiation/immunology
[MESH]
|Cells, Cultured
[MESH]
|Chemokine CCL2/*physiology
[MESH]
|Coculture Techniques
[MESH]
|Dendritic Cells/immunology
[MESH]
|Graft vs Host Disease/*immunology/metabolism
[MESH]