Adherence to endothelium, connective tissue or extracellular matrices is likely to play a critical role in triggering monocyte activation in extravascular sites of infection, tissue destruction and neoplastic growth. We have recently shown that within 20 mins of monocyte adherence, a complex set of regulatory events is initiated as evidenced by rapid changes in steady-state mRNA levels; these include suppression of genes coding for c-fms and lysozyme and rapid but transient induction of c-fos, TNF- and lL- lB. Two dimensional gel analysis demonstrated that at least 40 new proteins are expressed as a result of adherence. Furthermore, initial studies indicate that adherence to different extracellular matrices, endothelial and stromal cells have characteristic induction patterns which are subsets of that found on plastic adherence. We believe that the sequential and ordered development of the inflammatory macrophage in different sites is triggered by these early adherence interactions. In order to analyze these molecular events in regulation, we have constructed a cDNA library from monocytes adhered for 30 mins. From this, following subtraction and differential hybridization, 15 unique clones have already been isolated. Preliminary DNA sequencing indicates that none of the first 6 cDNA clones share close sequence similarity with known genes and are differentially regulated. As interaction of monocyte with the extracellular matrices is believed to be critical in maintaining the chronic inflammatory cascade, we will concentrate on defining those genes associated with transcriptional activation on collagen.
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