Pseudomonas aeruginosa exoenzyme S stimulates murine lymphocyte proliferation in vitro

The exuberant immunoinflammatory response that is associated with Pseudomon as aeruginosa infection is the major source of the morbidity and mortality in cystic fibrosis (CF) patients. Previous studies have established that an exoproduct of P. aeruginosa (exoenzyme S) is a mitogen for human T lymphoc ytes and activates a larger percentage of T cells than most superantigens, which may contribute to the immunoinflammatory response. An animal model wo uld facilitate studies of the pathophysiologic consequences of this activat ion. As a first step toward developing an animal model, the murine lymphocy te response to exoenzyme S was examined. When stimulated with exoenzyme S, splenocytes isolated from naive mice entered S phase and proliferated. The optimum response occurred after 2 to 3 days in culture, at 4 x 10(5) cells per well and 5.0 mu g of exoenzyme S per mi, The response was not due to li popolysaccharide, since Rhodobacter sphaeroides lipid A antagonist did not block the response. Other preparations of exoenzyme S stimulated lymphocyte proliferation, since the response to recombinant exoenzyme S (rHisExo S) c loned from strain 388 was similar to the response to exoenzyme S from strai n DG1. There was evidence that genetic variability influenced the response, since A/J, CBA/J, and C57BL/6 mice were high responders and BALB/cJ mice w ere low responders following stimulation with exoenzyme S, Both splenic T a nd B lymphocytes entered the cell cycle in response to exoenzyme S. Thus, m urine lymphocytes, like human lymphocytes, respond to P. aeruginosa exoenzy me S, which supports the development of a murine model that may facilitate our understanding of the role that exoenzyme S plays in the pathogenesis of P. aeruginosa infections in CF patients.