Physiological activation of human neutrophils down-regulates CD53 cell surface antigen

Tetraspanin transmembrane proteins have a metastasis suppressor effect by acting as cell motility brakes in tumor cells. CD53 is a panleukocyte antigen that belongs to the tetra-span superfamily. Human neutrophils express high levels of CD53. We tested the hypothesis that this antigen level changes when cells are activated. Treatment of human neutrophils with their physiological activators, tumor necrosis factor alpha or platelet-activating factor, resulted in down-regulation of this antigen from the cell surface, as assessed by immunofluorescence flow cytometry. Similar responses were observed when neutrophils were stimulated with chemotactic N-formyl-methionyl-leucyl-phenylalanine, phorbol ester, or the calcium ionophore ionomycin. The CD53 antigen down-regulation upon neutrophil stimulation was further confirmed by immunoblotting analysis and was not correlated with a change in the level of CD53 transcripts. This CD53 antigen down-regulation paralleled that of CD43 and CD44 antigens in these cells, despite their different protein structure. The down-regulation of the three antigens CD53, CD43, and CD44 could be inhibited by phenylmethylsulfonyl fluoride, suggesting that CD53 antigen down-regulation is the result of the activation of a proteolytic mechanism. Down-regulation of CD53 antigen level, as a result of cellular stimulation, might play a role in the different aspects of neutrophil biology, by modulating its interactions on the cell surface.