Beta 1 integrins mediate adherent phenotype of human erythroblastic cell lines after phorbol 12-myristate 13-acetate induction.
We investigated the effects of phorbol ester (phorbol 12-myristate 13-acetate; PMA) treatment on the adhesive behaviour of three erythroleukaemia cell lines: HEL, LAMA-84 and AP217. In the three cell lines PMA induced an increase in expression of a megakaryocytic marker: alpha IIb beta 3 integrin, but did not promote activation of this receptor. Indeed, an antibody specific for the activated form of alpha IIb beta 3 failed to react with the three cell lines. PMA induction led to different adhesive phenotypes depending on the cell line; in fact LAMA-84 and HEL cells became adherent while AP217 cells remained non-adherent. By studying cell surface receptors we found that the major difference between the adherent and the non-adherent cells was the expression of beta 1 integrins. After PMA induction, beta 1 integrin expression was totally abolished in AP217 cells and the amount of beta 1 mRNA was reduced preventing new synthesis of the subunit. In HEL and LAMA-84 cells, PMA treatment did not alter the overall level of beta 1 integrin but induced a new pattern of alpha-subunit expression: up-regulation of alpha 2 and alpha v subunits and down-regulation of alpha 4 and alpha 5 subunits. Function-perturbing antibodies against beta 1, alpha 4, alpha 5, alpha v and alpha 2 reduced adhesion of HEL cells to fibronectin or collagen, whereas antibodies against beta 3 or alpha v beta 3 did not. Our results favour the involvement of beta 1 integrins in PMA-induced adhesion of erythroleukaemia cells.
Molla
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A
Institut National de la Sante et de la Recherche Medicale Unite 217, Centre d'Etudes Nucleaires, Grenoble, France.
Berthier
R
R
Chapel
A
A
Schweitzer
A
A
Andrieux
A
A
D001483:Base Sequence; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers; D015536:Down-Regulation; D004912:Erythrocytes / Q000187:drug effects* / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D017931:DNA Primers; D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate