<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>Abstract
Keratinocytes were shown to induce the activation of plasminogen activator resulting in
the formation of plasmin and the initiation of proteolysis <italic>in vitro</italic>. Activation of surface
bound plasminogen may localize protease activity in the pericellular microenvironment
and play a role in inducing both a conformational change and cell locomotion. Plasmin,
however, can induce non-proteolytic effects on certain cell functions in a variety of cell
lineages. In the present study we examined the effects of plasmin on keratinocytes with
a focus on its role in the process of re-epithelialization, which included studies of cell
migration, phagocytic-killing and cell proliferation. Migration of freshly isolated human
epidermal keratinocytes was analyzed utilizing the agarose gel assay in the presence of
10% human serum. Plasmin at the concentration of 25 U/l induced a 160% increase in
the chemotactic migration of keratinocytes that was completely blocked by the plasmin
inhibitor α<sub>2</sub>-antiplasmin (Serpin). In the absence of serum, plasmin also induced a reversible
chemotactic migration of HaCaT keratinocytes as determined utilizing the microchemotaxis
assay. Dose-response analysis showed a bi-phasic effect of plasmin with a maximum
increase of 52% in keratinocyte chemotaxis at a concentration of 25 U/l. HaCaT cells on
the other hand, showed no detectable <italic>in vitro</italic> chemokinesis by
plasmin. Phagocytic-killing
of Candida albicans by freshly isolated epidermal keratinocytes was enhanced in the
presence of 25 U/l plasmin which was also reversible by the addition of Serpin.
Spontaneous proliferation of HaCaT keratinocytes as determined by <sup>3</sup>H-Thymidine uptake
on the other hand, was reduced by 47 and 13% in cultures with 25 U/l plasmin for 24 and
48 h respectively, in a Serpin reversible manner. These data suggest that plasmin-induced
chemotactic migration of epidermal keratinocytes is accompanied by enhanced
phagocytic-killing coupled with suppression of proliferation of these cells which may
facilitate re-epithelialization following skin injury.</p>
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Clin Dev Immunol. 2004 Sep-Dec; 11(3-4):233-240