Production and release of macrophage migration inhibitory factor from human adipocytes.
OBJECTIVE
Macrophage migration inhibitory factor (MIF) has been identified as a critical mediator of inflammatory responses. Because of its potent migration inhibition activity, it regulates macrophage accumulation in tissues. We therefore analyzed whether human adipocytes produce MIF, in the search of candidate mediators of macrophage infiltration of obese adipose tissue.


METHODS
Human adipose tissue samples were obtained from various depots. The precursor cells were allowed to differentiate under defined adipogenic culture conditions. MIF expression was analyzed by RT-PCR, ELISA, and immunocytochemistry.


RESULTS
Human preadipocytes secreted MIF in a differentiation-dependent fashion with maximum concentrations at d 12, whereas MIF mRNA was detected in both undifferentiated and differentiated cells at relatively constant levels. Immunocytochemical analysis showed that MIF protein was present in preadipocytes and more pronounced in differentiated adipocytes. Freshly isolated mature adipocytes from sc, omental, and mammary depots released MIF at rates of up to 10,000 pg/ml.24 h. Most importantly, MIF production was positively correlated with donor body mass index. Secretion of MIF was not influenced by lipopolysaccharide, interferon-gamma, or IL-4. The rates of MIF release from sc and omental adipocytes were similar but approximately 10 times higher compared with mammary adipocytes.


CONCLUSIONS
Human preadipocytes and mature adipocytes from different depots spontaneously release substantial amounts of MIF. Expression levels were positively associated with donor body mass index. Hence, MIF may be an obesity-dependent mediator of macrophage infiltration of adipose tissue.
Skurk
Thomas
T
Else Kröner-Fresenius Centre for Nutritional Medicine, Technical University Munich, Hochfeldweg 1, D-85350 Freising/Weihenstephan. skurk@wzw.tum.de
Herder
Christian
C
Kräft
Ilka
I
Müller-Scholze
Sylvia
S
Hauner
Hans
H
Kolb
Hubert
H
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002454:Cell Differentiation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis* / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma