Functional immaturity of cord blood monocytes as detected by impaired response to hepatocyte growth factor.
BACKGROUND
Monocytes as antigen-presenting cells play an important role in host defense and transplantation. However, there are little reports on cord blood monocytes, and the role of monocytes in cord blood transplantation is largely unknown.


RESULTS
There are several cytokines affecting monocyte function. These include interferon-gamma, interleukin-4, interleukin-10, granulocyte macrophage-colony stimulating factor and hepatocyte growth factor (HGF). We investigated the effect of these cytokines on antigen-presenting capacity (APC) of cord and adult blood monocytes. Using either mononuclear cells or purified CD4+ T cells as responder cells, HGF enhanced APC of adult monocytes most effectively among these cytokines. In contrast, cord blood monocytes failed to respond to HGF. As HLA, costimulatory and adhesion molecules may affect APC function, we examined these antigens of monocytes following HGF stimulation. The HGF upregulated integrin alpha5 subunit (CD49e) and intercellular adhesion molecule-1 (CD54) was expressed in adult blood monocytes, but not in cord blood. In kinetic studies, HGF downregulated c-met protein/HGF receptor expression of adult monocytes in lower concentrations and at shorter incubation time as compared with that of cord blood.


CONCLUSIONS
The results suggest that impaired response of cord blood monocytes to HGF may be responsible, in large part, for their functional immaturity.
Jiang
Q
Q
Department of Pediatrics and Clinical Immunology, Mie University School of Medicine, Japan.
Azuma
E
E
Hirayama
M
M
Iwamoto
S
S
Kumamoto
T
T
Kobayashi
M
M
Yamamoto
H
H
Sakurai
M
M
Komada
Y
Y
D000328:Adult; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000276:immunology*; D006801:Humans; D039482:Integrin alpha5; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D039482:Integrin alpha5; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D015534:Trans-Activators; D018799:Intercellular Adhesion Molecule-1; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met