An aminopeptidase regulates LPS stimulated interleukin-8 receptor on the surface of human neutrophils

A large number of inflammatory diseases are mediated by interleukin-8, an inflammatory neutrophil chemotactic agent. Since the cytokine acts through a cell surface receptor, detailed knowledge about the regulation of receptor expression is very important. We found that LPS in serum became activated and triggered the expression of IL-8 receptor by more than two folds within 30 min. After that period, the receptor attained normal level within 2 hr of SA-LPS stimulation. EDTA and bestatin could block this Ca2+ level was increased till 45 min of SA-LPS stimulation downregulation of IL-8 receptor. Intracellular Ca2+ inhibited the and then the level was reduced. Addition of CaCl2 accelerated and depletion of Ca2+ downregulaion of the IL-8 receptor. The ligand could fully protect the loss of receptor from downregulation. It suggests that during SA-LPS stimulation, increase in intracellular Ca2+ level activates an aminopeptidase which presumably cleaves the N-terminal region of the receptor, critically essential for the function of IL-8. Thus the activated aminopeptidase regulates the functions of IL-8. The study is important for understanding the regulation of IL-8 receptor expression by LPS during bacterial infection.