Production of Soluble Granulocyte Colony-Stimulating Factor Receptors from Myelomonocytic Cells

Author:

Iwasaki Hiromi1,Shimoda Kazuya1,Okamura Seiichi1,Otsuka Teruhisa1,Nagafuji Koji1,Harada Naoki1,Ohno Yuju1,Miyamoto Toshihiro1,Akashi Koichi1,Harada Mine2,Niho Yoshiyuki1

Affiliation:

1. *First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan; and

2. †Second Department of Internal Medicine, Okayama University School of Medicine, Okayama, Japan

Abstract

AbstractIt has been speculated that a soluble form of G-CSFR might be physiologically present in humans, since G-CSFR mRNA that lacks a transmembrane domain has been identified from a human myelomonocytic cell line. Here, we demonstrate human soluble G-CSFR (sG-CSFR) of two different molecular sizes (80 and 85 kDa) on an immunoblot analysis using Abs generated against the amino-terminal, extracellular domain of the full-length G-CSFR. Both isoforms of sG-CSFR were able to bind recombinant human G-CSF (rhG-CSF). RT-PCR analysis with primers targeted outside of the transmenbrane region revealed that membrane-anchored G-CSFR is expressed at all maturation stages of purified myeloid cells, including CD34+CD13+ cells (blasts), CD11b−CD15+ cells (promyelocytes or myelocytes), CD11b+CD15+ cells (metamyelocytes and mature neutrophils), and CD14+ cells (monocytes). On the other hand, sG-CSFR mRNA was detectable in CD11b−CD15+, CD11b+CD15+, and CD14+ cells, but not in the CD34+CD13+ blast population. The serum concentration of both isoforms of sG-CSFR appeared to be correlated with the numbers of neutrophils/monocytes before and after rhG-CSF treatment in normal individuals. Thus, two isoforms of sG-CSFR are physiologically secreted from relatively mature myeloid cells and might play an important role in myelopoiesis through their binding to serum G-CSF.

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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