EXPRESSION OF INTEGRINS AND BASEMENT-MEMBRANE COMPONENTS BY WOUND KERATINOCYTES

Extracellular matrix proteins and their cellular receptors, integrins, play a fundamental role in keratinocyte adhesion and migration. Durin g wound healing, keratinocytes detach, migrate until the two epithelia l sheets confront, and then regenerate the basement membrane. We exami ned the expression of different integrins and their putative ligands i n keratinocytes during human mucosal wound healing. Migrating keratino cytes continuously expressed kalinin but not the other typical compone nts of the basement membrane zone: type IV collagen, laminin, and type VII collagen. When the epithelial sheets confronted each other, these missing basement membrane components started to appear gradually thro ugh the entire wound area. The expression of integrin beta1 subunit wa s increased in keratinocytes during migration. The beta1-associated al pha2 and alpha3 subunits were expressed constantly by wound keratinocy tes whereas the alpha5 subunit was present only in keratinocytes durin g reepithelialization. Furthermore, migrating cells started to express alpha(v)-integrins which were not present in the nonaffected epitheli um. All keratinocytes also expressed the alpha6beta4 integrin during m igration. In the migrating cells, the distribution of integrins was al tered. In normal mucosa, beta1-integrins were located mainly on the la teral plasma membrane and alpha6beta4 at the basal surface of basal ke ratinocytes in the nonaffected tissue. In wounds, integrins were found in filopodia of migrating keratinocytes, and also surrounding cells i n several cell layers of the migrating sheet. The results indicate tha t migrating keratinocytes in deep human wounds enlarge their integrin repertoire. The changes in integrin expression take place concomitantl y with changes in the basement membrane composition, suggesting a clos e interplay of these two groups of molecules during wound healing.