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 panleukoc yte antigen that belongs to the tetra-span superfamily, Human neutroph ils express high levels of CD53, We tested the hypothesis that this an tigen level changes when cells are activated. Treatment of human neutr ophils with their physiological activators, tumor necrosis factor alph a or platelet-activating factor, resulted in down-regulation of this a ntigen from the cell surface, as assessed by immunofluorescence flow c ytometry similar responses were observed when neutrophils were stimula ted,vith chemotactic N-formyl-methionyl-leucyl-phenylalanine, phorbol ester, or the calcium ionophore ionomycin, The CD53 antigen down-regul ation upon neutrophil stimulation Tvas further confirmed by immunoblot ting analysis and,vas not correlated with a change in the level of CD5 3 transcripts, This CD53 antigen down-regulation paralleled that of CD 43 and CD44 antigens in these cells, despite their different protein s tructure. The down-regulation of the three antigens CD53, CD43, and CD 44 could be inhibited by phenylmethylsulfonyl fluoride, suggesting tha t CD53 antigen down-regulation is the result of the activation of a pr oteolytic mechanism, Down-regulation of CD53 antigen level, as a resul t of cellular stimulation, might play a role in the different aspects of neutrophil biology, by modulating its interactions on the cell surf ace.