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Distinct types of fibrocyte can differentiate from mononuclear cells in the presence and absence of serum.

ABSTRACT: Fibrocytes are bone-marrow derived cells, expressing both haematopoietic and stromal cell markers, which contribute to tissue repair as well as pathological fibrosis. The differentiation of fibrocytes remains poorly characterised and this has limited understanding of their biology and function. In particular two methods are used to generate fibrocytes in vitro that differ fundamentally by the presence or absence of serum.We show here that fibrocytes grown in the absence of serum (SF) differentiate more efficiently from peripheral blood mononuclear cells than CD14(+) monocytes, and respond to serum by losing their spindle-shaped fibrocyte morphology. Although fibrocytes generated in the presence of serum (SC) express the same range of markers, they differentiate more efficiently from CD14(+) monocytes and do not change their morphology in response to serum. Transcriptional analysis revealed that both types of fibrocyte are distinct from each other, fibroblasts and additional monocyte-derived progeny. The gene pathways that differ significantly between SF and SC fibrocytes include those involved in cell migration, immune responses and response to wounding.These data show that SF and SC fibrocytes are distinct but related cell types, and suggest that they will play different roles during tissue repair and fibrosis where changes in serum proteins may occur.

SUBMITTER: Curnow SJ

PROVIDER: S-EPMC2841180 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Distinct types of fibrocyte can differentiate from mononuclear cells in the presence and absence of serum.

Curnow S John SJ Fairclough Marianne M Schmutz Caroline C Kissane Steve S Denniston Alastair K O AK Nash Kate K Buckley Christopher D CD Lord Janet M JM Salmon Mike M

PloS one 20100318 3

<h4>Background</h4>Fibrocytes are bone-marrow derived cells, expressing both haematopoietic and stromal cell markers, which contribute to tissue repair as well as pathological fibrosis. The differentiation of fibrocytes remains poorly characterised and this has limited understanding of their biology and function. In particular two methods are used to generate fibrocytes in vitro that differ fundamentally by the presence or absence of serum.<h4>Methodology/principal findings</h4>We show here that ...[more]

PMID: 20305780

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Project description:BackgroundLatent autoimmune diabetes in adults (LADA) is characterized by autoimmunity, late-onset and intermediate beta-cell deprivation rate between type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM). Herein, we investigated proinsulin (PI) secretion patterns and the endoplasmic reticulum (ER) dysfunction biomarker, PI-to-C-peptide (PI:CP) ratio, to elucidate beta-cell intrinsic pathogenesis mechanisms in different types of diabetes.MethodsTotal serum fasting PI (FPI) were measured in adult-onset and newly-diagnosed diabetes patients, including 60 T1DM, 60 LADA and 60 T2DM. Thirty of each type underwent mixed meal tolerance tests (MMTTs), and hence 120 min postprandial PI (PPI) were detected. PI:CP ratio = PI (pmol/L) ÷ CP (pmol/L) × 100%. PI-related measurements among types of diabetes were compared. Correlation between PI-related measurements and beta-cell autoimmunity were analyzed. The possibility of discriminating LADA from T1DM and T2DM with PI-related measurements were tested.ResultsFPI and PPI were significantly higher in LADA than T1DM (P<0.001 for both comparisons), but lower than those in T2DM (P<0.001 and P=0.026, respectively). Fasting PI:CP ratio was significantly higher in T1DM than both LADA and T2DM (median 3.25% vs. 2.13% and 2.32%, P=0.011 and P=0.017, respectively). In LADA, positive autoantibody numbers increased by both fasting and postprandial PI:CP ratio (P=0.007 and P=0.034, respectively). Areas under receiver operation characteristic curves (AUCROC) of FPI and PPI for discriminating LADA from adult-onset T1DM were 0.751 (P<0.001) and 0.838 (P<0.001), respectively. Between LADA and T2DM, AUCROC of FPI and PPI were 0.685 (P<0.001) and 0.741 (P=0.001), respectively.ConclusionsIn the development of autoimmune diabetes, interplays between ER stress and beta-cell autoimmunity are potentially responsible for severer beta-cell destruction. PI-related measurements could help in differentiating LADA from adult-onset T1DM and T2DM.

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Distinct types of fibrocyte can differentiate from mononuclear cells in the presence and absence of serum.

Publications

Distinct types of fibrocyte can differentiate from mononuclear cells in the presence and absence of serum.

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