Original Paper

Differential Regulation of Insulin-Like Growth Factor-(IGF) I and IGF-Binding Protein (IGFBP) Secretion by Human Peripheral Blood Mononuclear Cells
C.J. Auernhammer^a, C. Fottner^b, D. Engelhardt^a, M. Bidlingmaier^c, C.J. Strasburger^c, M.M. Weber<sup>b

a</sup>Medizinische Klinik II Klinikum Grosshadern and
^bMedizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität München, and
^cLehrstuhl II für Innere Medizin der Universität zu Köln, Klinikum Merheim, Cologne, Germany

Address of Corresponding Author

Horm Res 2002;57:15-21 (DOI: 10.1159/000057941)

  Key Words

• Insulin-like growth factor
• IGF-I
• IGF-binding proteins
• 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.

Copyright © 2002 S. Karger AG, Basel

  Author Contacts

Priv.-Doz. Dr. Matthias M. Weber
Lehrstuhl II für Innere Medizin der Universität zu Köln
Medizinische Universitätsklinik Köln-Merheim
Ostmerheimerstrasse 200, D-51109 Köln (Germany)
Tel. +49 221 8907 3820, Fax +49 221 8907 3488, E-Mail MMWeber@t-online.de

  Article Information

Received: Received: March 23, 2001
Accepted after revision: November 16, 2001
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 0, Number of References : 36