Amphiregulin (AR) is a recently discovered menber of the EGF-receptor- binding family of ligands that also includes Epidermal Growth Factor (EGF), Transforming Growth Factor-alpha (TGF-a), Heregulin (HR), and Heparin-binding EGF (HB-EGF). The biological explanation for the ostensible redundancy within this family is unclear; however, emerging experimental data suggest principally a proliferative function for EGF and TGF-alpha, and a differentiative one for AR, HR, and HB-EGF. Using the Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) technique to semi-quantify AR mRNA, freshly isolated human monocytes expressed AR in a time-dependent manner following induction with either lipopolysaccaride or physiologic concentrations of platelate releasate. Interestingly, neither mRNA for TGF-a by RT-PCR, nor EGF-receptor expression by kinase phosphorylation assays, was detected in induced monocytes. AR was also associated by immunocytochemistry to monocytes, and by immunohistochemistry of human venous stasis ulcers in which AR staining was detected mainly in vascular cuffs and at wound margins where active epithelial proliferation was evident. Platelate releasate derives from the alpha-granules of platelates, and contributes to the main mileau of the initial phase of wound healing. Which individual components of platelate releasate are responsible for AR mRNA induction, and whether or not AR protein is anchored to monocyte cell membranes or is secreted in its glycosylated form, are currently under investigation.
