Healing of full-thickness cutaneous wounds in the pig. I. Immunohistochemical study of epidermo-dermal junction regeneration.

ABSTRACT

In order to determine the kinetics of epidermo-dermal junction (EDJ) regeneration during would healing, we studied the regeneration of five EDJ components during reepidermization. Cutaneous wounds (50-mm length, 2-mm width, and 5-mm depth) were produced on the flank area of two pigs and left unsutured. Daily biopsies from day 1 to day 20 were studied by light microscopy on paraffin-embedded sections and by indirect immunofluorescence on cryostat sections using human sera to bullous pemphigoid antigen (BPA) with specificity previously confirmed by indirect immuno-electron microscopy, rabbit antisera to type IV collagen (Coll IV) and to fibronectin, and the monoclonal antibodies (MoAb) 4C 12-8 to laminin and NP-76 to type VII collagen (Coll VII). Histologically, reepidermization started from day 1 and progressed unidirectionally and exclusively from the wound edges. Up to day 9, the distal tips of the neo-epidermal tongues generally extended between the crust and the granulation tissue (GT). They fused on day 10, restoring epidermal continuity. For each EDJ component, the date of appearance (emergence), the spreading under the neo-epidermis tongue (expression), and the morphologic aspect of the labeling were studied. BPA and Coll IV were detected from day 1 to day 20 and found to be expressed all along the neo-EDJ. Fibronectin and laminin were detected from day 1, were present in the proximal and median zones of the neo-EDJ before day 7, up to the distal tip from day 7 to day 9 and were all along the neo-EDJ from day 10 to day 20. Coll VII was only detected from day 3. It was present in the proximal zone on day 3 and day 4, in the proximal and median zones on day 5 and day 6, than all along the neo-EDJ from day 7 to day 20. From day 10, all the labeling characteristics of the five components were found to be similar in the neo-EDJ and in the normal EDJ. With regard to the neo-epidermis progression, we found a synchronism of emergence and expression for BPA and Coll IV, a synchronism of emergence but a delay of expression for fibronectin and laminin and lastly, a delay of emergence and expression for Coll VII. We concluded that BPA and Coll IV could constitute the framework on which the neo-EDJ is progressively built by adjunction of the other components, restitution being obtained just after epidermal continuity is restored.