Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes.
Adherence is an important regulatory signal for several monokines and the proto-oncogenes c-fms and c-fos in human peripheral blood monocytes. Although there is little if any constitutive expression of the IL-1 beta, TNF-alpha and CSF-1 genes in freshly isolated monocytes, adherence is sufficient to induce high steady-state levels of mRNA for TNF and c-fos and more slowly that of CSF-1. Expression of mRNA for the CSF-1R gene, c-fms, was transiently down-regulated by 4 h. In contrast, the induction of high levels of IL-1 beta mRNA were achieved independent of culture conditions. Although all of these genes could be induced by adherence, actual secretion of the mediators required the exposure to a second signal derived from LPS. Thus adherence rapidly primes monocytes for a variety of inflammatory responses, the magnitude of which depends on the nature of a second "activating" signal. It is likely that some of these products act locally as paracrine or autocrine factors to further regulate the phenotype of the differentiating macrophage.
Haskill
S
S
Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill 27599.
Johnson
C
C
Eierman
D
D
Becker
S
S
Warren
K
K
D002448:Cell Adhesion / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism / Q000502:physiology*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha