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Differential Expression of M‐CSF, G‐CSF, and GM‐CSF by Human Monocytes
Author(s) -
Lee MeiTing,
Kaushansky Kenneth,
Ralph Peter,
Ladner Martha B.
Publication year - 1990
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.47.3.275
Subject(s) - biology , secretion , lipopolysaccharide , monocyte , endocrinology , colony stimulating factor , medicine , macrophage colony stimulating factor , prostaglandin e2 , prostaglandin e , granulocyte macrophage colony stimulating factor , prostaglandin , cytokine , microbiology and biotechnology , immunology , macrophage , in vitro , biochemistry , haematopoiesis , stem cell
The colony‐stimulating factors (CSF) belong to a group of proteins which regulate blood cell production. Human monocytes allowed to adhere express high levels of M‐CSF transcripts and secreted protein at 24 h in the presence but not in the absence of indomethacin (Indo), an inhibitor of prostaglandin E (PGE) production. When induced with lipopolysaccharide (LPS), adherent monocytes express M‐CSF, G‐CSF, and GM‐CSF transcripts and secrete these proteins and TNF. M‐CSF and GM‐CSF messages increase in LPS‐induced monocytes by the addition of Indo, while G‐CSF mRNA appears to decrease. Exogenous addition of PGE‐2 to LPS‐induced monocytes down‐modulates the expression of M‐CSF and GM‐CSF transcripts. G‐CSF message is elevated, suggesting an alternate pathway to G‐CSF regulation. PGE‐2 inhibits the secretion of CSFs and TNF. In contrast, LPS‐induced monocytes held 24 h in nonadherent culture express G‐ and GM‐CSF but not M‐CSF. Monocytes that are adhered for 24 h and then treated with LPS for an additional 24 h express only M‐CSF message and secrete M‐CSF and TNF. PGE‐2 added with LPS during the 24–48 h induction blocks M‐CSF and TNF production, but appears to enhance M‐CSF message expression, in contrast to its effect on 0 h inductions. These results suggest that adherence alone induces M‐CSF gene expression, but low levels of PGE or other arachidonic acid metabolites limit this expression. Other events in 1 d‐cultured monocytes block the ability to induce G‐CSF and GM‐CSF expression with LPS, and block the suppressive effect of PGE‐2 on M‐CSF expression at the RNA level.