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Response of epidermolysis bullosa fibroblasts to factors derived from macrophages and polymorphonuclear leukocytes in terms of collagenase production.

In order to investigate the role of inflammatory cells in altering the collagenase production by epidermolysis bullosa (EB) fibroblasts, macrophage and polymorphonuclear leukocyte (PMN) factors obtained from mouse peritoneal fluids were added to the fibroblast culture system, and collagenase activity was assayed after a 48-h incubation. Data obtained here revealed that the response of collagenase production by fibroblasts was quite different, depending on the type of EB. Namely, EB dystrophica recessiva (EBDR) (n = 2) fibroblasts produced significant amounts of collagenase in the range of 5.07 (U/ml) to 6.04 in response to macrophage-conditioned medium, macrophage lysate, and PMN lysate, compared with 0.13 in the absence of these. On the other hand, EB dystrophica dominans (EBDD) (n = 1) fibroblasts showed little or no overt increase in enzyme production in the presence of macrophage lysate and PMN lysate, which resulted in a moderate increase to 3.82 in response to macrophage-conditioned medium. Furthermore, EB simplex (EBS) (n = 1) fibroblasts produced collagenase up to 3.84 in response to these three factors. These factors can be inactivated by treating with trypsin, pronase, and phenylglyoxal. Our data clearly indicated that, in the comparisons of EBDD and EBS fibroblasts, EBDR fibroblasts showed quite high response to factors derived from macrophages and PMNs in terms of collagenase production. This fact may raise a clue that accounts for the high levels of tissue collagenase activity, which plays a potentially major role in blister formation in EBDR.