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 downregulation of IL-8 receptor. Intracellular Ca2+ level was increased till 45 min of SA-LPS stimulation and then the level was reduced. Addition of CaCl2 accelerated and depletion of Ca2+ inhibited the downregulation 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.
Bhattacharya
C
C
Division of Biometry, Indian Statistical Institute, Calcutta, India.
Manna
S K
SK
Samanta
S
S
Gupta
S K
SK
Samanta
A K
AK
D000626:Aminopeptidases / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D001424:Bacterial Infections / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D023062:Receptors, Interleukin-8A
D015703:Antigens, CD; D008070:Lipopolysaccharides; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D000626:Aminopeptidases; D002118:Calcium