Differential Regulation of Insulin-Like Growth Factor-(IGF) I and IGF-Binding Protein (IGFBP) Secretion by Human Peripheral Blood Mononuclear Cells

Abstract

Background: Recent studies have shown that immunocompetent cells synthesize and express growth hormone (GH), growth hormone receptors (GH-R), insulin-like growth factor I (IGF-I), IGF-I receptors (IGF-I-R) and different insulin-like growth factor binding proteins (IGFBPs). The aim of the current study was to evaluate the regulation of IGFBP and IGF-I secretion from immunocompetent cells by different mitogens. Methods/Results: We studied the in vitro secretion pattern of IGFBPs and IGF-I from human peripheral blood mononuclear cells (PBMC), derived from 10 normal adults and 8 GH-deficient patients with adult onset. In serum-free conditioned medium of unstimulated PBMC, derived from normal adults, Western ligand blotting (1D-WLB) revealed a 24-kD, a 34-kD and a 39/43-kD doublet band to be most prominent. According to their molecular weight and two-dimensional Western ligand blot analysis (2D-WLB), these bands are deglycosylated IGFBP-4, IGFBP-2 and IGFBP-3, respectively. When the cells were treated with the T-cell mitogen phytohemagglutinin (PHA) (10 µg/ml), a differential stimulation of IGFBPs was found with a 2.57 ± 0.48-fold increase of IGFBP-4 (p < 0.01), a 1.55 ± 0.13-fold increase of IGFBP-2 (p < 0.01), and a 1.35 ± 0.19-fold increase of IGFBP-3 (n.s.). In contrast, treatment with the B-cell mitogen pokeweed mitogen (PWM) (10 µg/ml) caused only a modest 1.40 ± 0.07-fold increase of IGFBP-4 (p < 0.01). Treatment with rhGH (100 ng/ml) or rhIGF-I (200 ng/ml) caused no significant induction of any specific band, respectively. In contrast to the secretion pattern of IGFBPs, IGF-I secretion of the PBMC was not stimulated by either PHA or PWM, but showed a significant increase after GH incubation (p < 0.01). A similar differentiated secretion pattern of IGFBPs and IGF-I was also observed in the conditioned medium of PBMC, derived from GH-deficient patients. Conclusion: In summary, at least three different IGFBPs are secreted by human PBMC. Secretion of IGFBPs by PBMC is differentially regulated by different lymphocyte mitogens. Secretion of IGFBPs by PBMC is independent of GH or IGF-I, whereas the secretion of IGF-I is stimulated by GH. PBMC derived from normal adults and GH-deficient patients show similar patterns of IGF-I and IGFBPs secretion, thus indicating that the paracrine/autocrine IGF-I–IGFBPs interactions of the PBMC are not altered by pituitary GH deficiency.

C3 binding glycoprotein from Cuscuta europea induced different cytokine profiles from human PBMC compared to other plant and bacterial immunomodulators

“…Many authors have reported a different time point for culturing PBMC and other cells in serum-free media. For example, Auernhammer et al [33] have reported that unstimulated PBMC, derived from normal adult cultured in serum and growth factor free conditions, survived and produced insulin-like growth factor binding proteins (IGFBP-4, -3 and -2). Moreover, when the cells were stimulated with PHA or PWM, a differentiated secretion pattern of IGFBPs and IGF-1 was observed [33].…”

“…For example, Auernhammer et al [33] have reported that unstimulated PBMC, derived from normal adult cultured in serum and growth factor free conditions, survived and produced insulin-like growth factor binding proteins (IGFBP-4, -3 and -2). Moreover, when the cells were stimulated with PHA or PWM, a differentiated secretion pattern of IGFBPs and IGF-1 was observed [33]. Pilling et al found that CD14+ peripheral blood monocytes cultured in the absence of serum or plasma differentiate into fibrocytes within 72 h and purified serum amyloid inhibits fibrocyte differentiation [34].…”

Expression of insulin-like growth factor-I and insulin-like growth factor binding proteins during thioacetamide-induced liver cirrhosis in rats

“…The interface has been considered as an area with intensive inflammatory and reparative activity. Since inflammatory cells such as monocytes and macrophages are known to express IGFBP-3 [58], it is conceivable, although unproved by co-localization, that the high IGFBP-3 expression at the septal-nodular interface is caused by the inflammatory infiltration. However, in the center of the cirrhotic nodule IGFBP-3 mRNA specific grains were diminished.…”

Transcriptional response of peripheral blood mononuclear cells to recombinant human growth hormone in a routine four-days IGF-I generation test

“…Peripheral blood mononuclear cells (PBMCs) express the GHR and the IGF-IR [15] and are able to increase IGF-I production in vitro [16]. PBMC are easily accessible during routine blood sampling as part of a short-term four day IGFGT in children without the need of additional venipuncture.…”