ORIGINAL ARTICLES  CELLULAR AND MOLECULAR ADVANCES IN THE STUDY OF INFLAMMATION 

Minerva Biotecnologica 2004 June;16(2):127-33

Copyright © 2004 EDIZIONI MINERVA MEDICA

language: English

Inositide-modifying enzymes in differentiation of myeloid cells

Bertagnolo V. ¹, Brugnoli F. ¹, Bovolenta M. ¹, Capitani S. ^{1, 2}

¹ Signal Transduction Unit, Section of Human Anatomy Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy; ² MIUR ICSI (Interdisciplinary Center for the Study of Inflammation), University of Ferrara, Ferrara, Italy

Differentiation and ­response of neu­troph­ils to inflam­ma­to­ry stim­u­li con­sist of a com­plex ­sequence of ­events includ­ing cyto­skel­e­ton remod­el­ling and ­shape chang­es. While a num­ber of stud­ies per­formed ­with dif­fer­ent approach­es ­have indi­cat­ed the involve­ment of PLC and PI 3-K path­ways in a varie­ty of chem­o­at­trac­tant-­induced respons­es, the ­issue of wheth­er ­these inosi­tide-mod­i­fy­ing ­enzymes ­play a ­role ­also in mod­ulat­ing the phe­no­typ­ical mat­u­ra­tion pro­cess of inflam­ma­tion ­cells has not ­been ful­ly ­addressed. Recent ­work per­formed on mye­loid ­cells dem­on­strat­ed ­that the ­ATRA-­induced gra­nu­lo­cyt­ic mat­u­ra­tion of the HL-60 pro­myel­o­cyt­ic ­cell ­line, a ­well stud­ied mod­el of neu­troph­il-­like dif­fe­ren­ti­a­tion, is accom­pa­nied by the accu­mu­la­tion of spe­cif­ic iso­forms of PLC and PI 3-K ­inside the nucle­ar com­part­ment of dif­fer­en­tiat­ed ­cells. In par­tic­u­lar, it has ­been ­found ­that the activ­ity of PI 3-K, ­that ­appears to be essen­tial for the dif­fer­en­tia­tive pro­cess, is depen­dent on its inter­ac­tion ­with ­actin, in ­both cyto­plasm and nucle­ar com­part­ments of HL-60 ­cells. PI 3-K/­actin asso­ci­a­tion ­inside the nucle­us is medi­at­ed by tyro­sine phos­phor­y­lat­ed Vav, ­which may ­then be respon­sible of tar­get­ing PI 3-K to its nucle­ar ­matrix-asso­ciat­ed intra­nu­cle­ar sub­strates. Stemming ­from the ­notion ­that the chang­es in cyto­skel­e­ton assem­bly are reg­u­lat­ed by phos­phoi­no­si­tides, we ­review the ­data con­cern­ing the intra­nu­cle­ar expres­sion and activ­ity of spe­cif­ic inosi­tide-mod­i­fy­ing ­enzymes dur­ing dif­fe­ren­ti­a­tion of tumo­ral mye­loid pre­cur­sors. The col­lect­ed evi­denc­es sug­gest ­that chang­es of the intra­nu­cle­ar ­pool of phos­phoi­no­si­tides ­play key ­roles in the chang­es of the nucle­os­kele­ton ­that char­ac­ter­ize gra­nu­lo­cyt­ic mat­u­ra­tion.