EVIDENCE THAT SECONDARY MIXED LEUKOCYTE CULTURE SUPERNATANT MEDIATES CHANGES IN CELLULAR RECRUITMENT, BLOOD FLOW, AND VASCULAR PERMEABILITY

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Abstract
Lymphokines produced as a result of allostimulaation may play an important role in allograft rejection, mediating changes in cellular infiltration and migration, regional blood flow, and vascular permeability in a manner similar to that of delayed type hypersensitivity reactions. Changes in cellular recruitment (CR), regional blood flow (RBF), and vascular permeability (VP) were studied in paired healed subcutaneous urethane sponge grafts inoculated with secondary mixed leukocyte culture supernatant (2.degree. MLC SN), a rich source of a variety of lymphokines secreted in response to allostimulation. Intravenous injection of Indium-111-labeled unsensitized lymphocytes (UL), Rubidium-86-chloride, and Iodine-125-labeled albumin were used to assess CR, RBF, and VP, respectively. An increase in CR (P < 0.001), RBF (P < 0.05), and VP (P < 0.001) could be demonstrated at the site of injection of allogeneically restimulated 2.degree. MLC SN compared with the syngeneically restimulated 2.degree. MLC SN. The quantitative response and the kinetics of CR using 2.degree.MLC SN were similar to previous studies in which specifically sensitized lymphocytes were injected with target cells bearing the sensitizing alloantigen, but the increase in RBF and VP were less. Injection of purified human interleukin 2, serotonin, histamine, and bradykinin had no significant effect on CR. Injection of purified human interleukin 1 resulted in a moderate increase in CR. These results are consistent with previous studies suggesting that the in vivo elaboration of lymphokines during allogeneic cellular interactions leads to an increase in CR, RBF, and VP. The small changes in RBF and VP in these experiments, however, do not account for the greater magnitude of the changes in CR. It is likely that other specific or nonspecific chemoattractants or inhibitors of cell migration also play a significant role in CR in vivo.