Amphiregulin (AR) is a recently discovered member of the EGF-receptor-binding family of ligands that also includes, among others, Epidermal Growth Factor (EGF), Transforming Growth Factor-alpha (TGF-a), Heregulin (HRG), 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 freshly isolated human monocytes, AR mRNA was expressed in a time-dependent manner following induction with either lipopolysaccharide or physiologic concentrations of platelet releasate when examined with the differential RT-PCR technique. Interestingly, neither mRNA for TGF-a by RT-PCR, nor EGF-receptor expression by kinase phosphorylation assays, was detected in induced monocytes. However, this technique was neither truly quantitative nor reproducible. Currently, an RT-PCR approach for quantitating specific AR or TGF-a mRNA uses an internal RNA competitive reference standard, which is identical to the mRNA sequences of interest. 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. Platelet releasate derives from the alpha-granules of platelets, and contributes to the mileau of the initial phase of wound healing. Which individual components of platelet releasate are responsible for AR mRNA induction (e.g., perhaps PDGF or TGF-b), and whether or not AR protein is anchored to monocyte cell membranes or is secreted in its glycosylated form, are subjects for future investigation.
