scholarly journals Organic dust exposure alters monocyte-derived dendritic cell differentiation and maturation

2009 ◽  
Vol 297 (4) ◽  
pp. L767-L776 ◽  
Author(s):  
Jill A. Poole ◽  
Geoffrey M. Thiele ◽  
Neil E. Alexis ◽  
Angela M. Burrell ◽  
Conrad Parks ◽  
...  

Organic dust exposure in agricultural animal environments results in airway diseases. Dendritic cells (DCs) orchestrate inflammatory immune response in the airways, but little is known about how organic dust affects differentiation and maturation of monocyte-derived immature and mature DCs (iDCs, mDCs). Peripheral blood monocytes were differentiated in vitro into iDCs with granulocyte-macrophage colony stimulating factor + IL-4 (6 days) with and without swine facility organic dust extract (ODE, 0.1%). Unlike control iDCs, ODE-conditioned iDCs maintained key monocyte properties (increased mCD14, increased phagocytic ability) while expressing DC features [increased mCD83, HLA-DR, CD80, CD86, diminished cytokine (TNF-α, IL-6) responsiveness]. At day 6, iDCs were cultured for an additional 48 h ( days 7 and 8) with lipopolysaccharide (LPS) to induce mDCs. ODE-conditioned mDCs maintained high expression of mCD14+ and elevated phagocytosis while their DC features weakened as evidenced by decreased CD11c, CD83, HLA-DR, CD86, and CCR7 expression and reduced lymphocyte-stimulating capacity. Similar results were observed when monocytes were exposed to ODE for only the first 48 h and with ODE depleted of endotoxin. Control iDCs exposed to ODE during the final 2 days of iDC maturation ( days 7 and 8) did not differ from control (no ODE) iDCs in surface marker expression and phagocytic ability, but exhibited enhanced lymphocyte-stimulating capacity. Dust exposure alters monocyte differentiation to iDCs and prevents maturation of iDC to mDCs. The first 48 h of monocyte differentiation appears to be the susceptible period to exposure. Environmental exposures present during early monocyte differentiation may impact the critical balance of DCs in the lung.

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 788-795 ◽  
Author(s):  
JD Griffin ◽  
KD Sabbath ◽  
F Herrmann ◽  
P Larcom ◽  
K Nichols ◽  
...  

Abstract Expression of HLA-DR surface antigens by granulocyte/monocyte colony- forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. “Early” (day 14) CFU-GM express higher levels of HLA- DR than do “late” (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high- level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.


Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 145-151 ◽  
Author(s):  
RA Briddell ◽  
JE Brandt ◽  
JE Straneva ◽  
EF Srour ◽  
R Hoffman

Abstract Two classes of human marrow megakaryocyte progenitor cells are described. Colony-forming unit-megakaryocyte (CFU-MK)-derived colonies appeared in vitro after 12-day incubation; burst-forming unit- megakaryocyte (BFU-MK)-derived colonies appeared after 21 days. CFU-MK- derived colonies were primarily unifocal and composed of 11.6 +/- 1.2 cells/colony; BFU-MK-derived colonies were composed of 2.3 +/- 0.4 foci and 108.6 +/- 4.4 cells/colony. CFU-MK and BFU-MK were separable by counterflow centrifugal elutriation. CFU-MK colony formation was diminished by exposure to 5-fluorouracil (5-FU); BFU-MK colony formation was unaffected. CFU-MK and BFU-MK were immunologically phenotyped. CFU-MK expressed the human progenitor cell antigen-1 (HPCA- 1, CD34, clone My10) and a major histocompatibility class II locus, HLA- DR, and BFU-MK expressed only detectable amounts of CD34. BFU-MK colony formation was entirely dependent on addition of exogenous hematopoietic growth factors. Recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) possessed such colony- stimulating activity, whereas recombinant erythropoietin (Epo), G-CSF, IL-1 alpha, IL-4, and purified thrombocytopoiesis-stimulating factor did not. These studies indicate the existence of a human megakaryocyte progenitor cell, the BFU-MK, which has unique properties allowing it to be distinguished from the CFU-MK.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Nina L. Petrova ◽  
Peter K. Petrov ◽  
Michael E. Edmonds ◽  
Catherine M. Shanahan

We hypothesised that tumour necrosis factor-α(TNF-α) may enhance receptor activator of nuclear factor-κβligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and culturedin vitroon plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α(anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p>0.05), there was a significant increase in the area of resorption on the surface (p<0.01) and under the surface (p<0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-αresulted in a significant reduction in the area of resorption on the surface (p<0.05) and under the surface (p<0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-αmodulates RANKL-mediated osteoclastic resorptionin vitroin patients with acute Charcot osteoarthropathy.


Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1110-1116 ◽  
Author(s):  
HE Broxmeyer ◽  
B Sherry ◽  
L Lu ◽  
S Cooper ◽  
KO Oh ◽  
...  

Abstract Purified recombinant (r) macrophage inflammatory proteins (MIPs) 1 alpha, 1 beta, and 2 were assessed for effects on murine (mu) and human (hu) marrow colony-forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) colonies. Recombinant MIP-1 alpha, -1 beta, and -2 enhanced muCFU-GM colonies above that stimulated with 10 to 100 U natural mu macrophage-colony-stimulating factor (M-CSF) or rmuGM-CSF, with enhancement seen on huCFU-GM colony formation stimulated with suboptimal rhuM-CSF or rhuGM-CSF; effects were neutralized by respective MIP-specific antibodies. Macrophage inflammatory proteins had no effects on mu or huBFU-E colonies stimulated with erythropoietin (Epo). However, natural MIP-1 and rMIP-1 alpha, but not rMIP-1 beta or -2, suppressed muCFU-GM stimulated with pokeweed mitogen spleen-conditioned medium (PWMSCM), huCFU-GM stimulated with optimal rhuGM-CSF plus rhu interleukin-3 (IL-3), muBFU- E and multipotential progenitors (CFU-GEMM) stimulated with Epo plus PWMSCM, and huBFU-E and CFU-GEMM stimulated with Epo plus rhuIL-3 or rhuGM-CSF. The suppressive effects of natural MIP-1 and rMIP-1 alpha were also apparent on a population of BFU-E, CFU-GEMM, and CFU-GM present in cell-sorted fractions of human bone marrow (CD34 HLA-DR+) highly enriched for progenitors with cloning efficiencies of 42% to 75%. These results, along with our previous studies, suggest that MIP-1 alpha, -1 beta, and -2 may have direct myelopoietic enhancing activity for mature progenitors, while MIP-1 alpha may have direct suppressing activity for more immature progenitors.


Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1564-1569 ◽  
Author(s):  
A Spittler ◽  
S Winkler ◽  
P Gotzinger ◽  
R Oehler ◽  
M Willheim ◽  
...  

Reduced concentrations of glutamine (GLN) in plasma and skeletal muscle, defective host defense systems, and a diminished expression of the HLA-DR antigen on monocytes are important diagnostic parameters for late post-injury sepsis. In this in vitro study, we investigated whether blood monocyte-derived macrophage antigen expression and function from healthy donors is influenced by GLN. Lowering the GLN concentration in culture medium from 2 mmol/L to 200 mumol/L reduced the expression of HLA-DR by 40% (P &lt; .001) on monocyte-derived macrophages, and decreased tetanus toxoid-induced antigen presentation. In addition, low GLN levels downregulated the expression of intercellular adhesion molecule-1 (ICAM-1/CD54), Fc receptor for IgG (Fc gamma RI/CD64), and complement receptors type 3 (CR3; CD11b/CD18) and type 4 (CR4; CD11c/CD18). A correlation was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized Escherichia coli and the decreased expression of Fc gamma RI and CR3. Monocyte expression of CD14, CD71, and Fc gamma RIII/CD16 and capacity to phagocytose latex beads were not affected by altering the level of GLN. Depletion of GLN was associated with a significant reduction in cellular adenosine triphosphate (ATP), which may have influenced cell surface marker expression and phagocytosis. It remains to be seen whether these in vitro findings are of clinical significance in the treatment of sepsis.


Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1423-1431 ◽  
Author(s):  
James Chan ◽  
Pieter J.M. Leenen ◽  
Ivan Bertoncello ◽  
Shin-Ichi Nishikawa ◽  
John A. Hamilton

Abstract Macrophage populations resident in tissues and at sites of inflammation are heterogeneous and with local proliferation sometimes evident. Using the convenient murine peritoneal cavity as an inflammation model, the appearance of macrophage lineage cells was followed with time in both thioglycollate- and sodium periodate-induced exudates. The cells were characterized by their proliferative response in vitro in response to colony-stimulating factor-1 (CSF-1) (or macrophage colony-stimulating factor [M-CSF]), particularly by their ability to form colonies in agar, in combination with flow cytometry (surface marker expression and forward and side scatter characteristics). We propose that c-Fms (CSF-1 receptor), unlike other markers, is a uniformly expressed and specific marker suitable for the detection of macrophage-lineage cells in tissues, both in the steady state and after the initiation of an inflammatory reaction. It was shown that the bone marrow myeloid precursor markers, ER-MP58 and ER-MP20 (Ly-6C), but not ER-MP12 (PECAM-1), are expressed by a high proportion of macrophage-lineage cells in the inflamed peritoneum. The macrophage colony-forming cells (M-CFCs) in a 16-hour thioglycollate-induced exudate were phenotyped as c-Fms+ERMP12−20+58+, properties consistent with their being more mature than bone marrow M-CFCs. It is proposed that ER-MP58, as well as ER-MP20, may be a useful marker for distinguishing inflammatory macrophage-lineage cells from the majority of those residing normally in tissues. © 1998 by The American Society of Hematology.


1998 ◽  
Vol 6 (1-2) ◽  
pp. 25-39 ◽  
Author(s):  
Robert Gieseler ◽  
Dirk Heise ◽  
Afsaneh Soruri ◽  
Peter Schwartz ◽  
J. Hinrich Peters

Representing the most potent antigen-presenting cells, dendritic cells (DC) can now be generated from human blood monocytes. We recently presented a novel protocol employing GM-CSF, IL-4, and IFN-γto differentiate monocyte-derived DCin vitro. Here, such cells are characterized in detail. Cells in culture exhibited both dendritic and veiled morphologies, the former being adherent and the latter suspended. Phenotypically, they were CD1a-/dim, CD11a+, CD11b++, CD11c+, CD14dim/-, CD16a-/dim, CD18+, CD32dim/-, CD33+, CD40+, CD45R0+, CD50+, CD54+, CD64-/dim, CD68+, CD71+, CD80dim, CD86+/++, MHC class I++/+++HLA-DR++/+++HLA-DP+, and HLA-DQ+. The DC stimulated a strong allogeneic T-cell response, and further evidence for their autologous antigen-specific stimulation is discussed. Although resembling a mature CD 11c+CD45R0+blood DC subset identified earlier, their differentiation in the presence of the Thl and Th2 cytokines IFN-γand IL-4 indicates that these DC may conform to mature mucosal DC.


Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2668-2676 ◽  
Author(s):  
Beatriz León ◽  
Gloria Martínez del Hoyo ◽  
Verónica Parrillas ◽  
Héctor Hernández Vargas ◽  
Paloma Sánchez-Mateos ◽  
...  

Abstract The monocyte capacity to differentiate into dendritic cells (DCs) was originally demonstrated by human in vitro DC differentiation assays that have subsequently become the essential methodologic approach for the production of DCs to be used in DC-mediated cancer immunotherapy protocols. In addition, in vitro DC generation from monocytes is a powerful tool to study DC differentiation and maturation. However, whether DC differentiation from monocytes occurs in vivo remains controversial, and the physiologic counterparts of in vitro monocyte-derived DCs are unknown. In addition, information on murine monocytes and monocyte-derived DCs is scarce. Here we show that mouse bone marrow monocytes can be differentiated in vitro into DCs using similar conditions as those defined in humans, including in vitro cultures with granulocyte-macrophage colony-stimulating factor and interleukin 4 and reverse transendothelial migration assays. Importantly, we demonstrate that after in vivo transfer monocytes generate CD8- and CD8+ DCs in the spleen, but differentiate into macrophages on migration to the thoracic cavity. In conclusion, we support the hypothesis that monocytes generate DCs not only on entry into the lymph and migration to the lymph nodes as proposed, but also on extravasation from blood and homing to the spleen, suggesting that monocytes represent immediate precursors of lymphoid organ DCs. (Blood. 2004;103:2668-2676)


2008 ◽  
Vol 122 (2) ◽  
pp. 375-382.e4 ◽  
Author(s):  
Jill A. Poole ◽  
Neil E. Alexis ◽  
Conrad Parks ◽  
Amy K. MacInnes ◽  
Martha J. Gentry-Nielsen ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Anne Brosbøl-Ravnborg ◽  
Bettina Bundgaard ◽  
Per Höllsberg

Human dendritic cells (DC) can be differentiated from blood monocytes in the presence of GM-CSF and IL-4 and matured by lipopolysaccharide (LPS). Vitamin D3inhibits the maturation of human DC measured by changes in surface expression of HLA-DR, CD14, CD40, CD80, CD83, and CD86. We here examine the function of vitamin D3during DC maturation. One of the earliest changes to LPS-induced maturation was an increase in CD83 expression. Vitamin D3inhibited the increase in expression of HLA-DR, CD40, CD80, CD83, and CD86 and the decrease in expression of CD14, which was paralleled morphologically by vitamin D3-induced inhibition of dendritic cell differentiation. Vitamin D3acted in synergy with the TLR agonists LPS and peptidoglycan (PGN) in inducing IL-6, IL-8, and IL-10, whereas vitamin D3completely inhibited LPS-induced secretion of IL-12. The synergy occurred at concentrations where neither vitamin D3nor the TLR agonists alone induced measurable cytokine secretion. Both LPS and PGN enhanced the level of the vitamin D3receptor (VDR). Taken together, these data demonstrated that vitamin D3and TLR agonists acted in synergy to alter secretion of cytokines from human DC in a direction that may provide an anti-inflammatory environment.


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