Lymphoma cells contribute to the augmentation of plasma sL-selectins in the serum of lymphoma-bearing mice.

Abstract

Like many integral membrane glycoproteins, the extracellular domain of L-selectin undergoes rapid shedding, which occurs on both resting and activated host leucocytes. Incubating normal or transformed leukocytes with phorbol esters can also artificially induce shedding of L-selectin, providing multiple possibilities for the source of soluble forms of L-selectin found in the serum of patients with hematological malignancies. Here, using genetically engineered L-selectin-deficient mouse models, we have measured the release of soluble circulating forms of L-selectin in the serum of lymphoma-bearing mice. We found that L-selectin-deficient lymphoma cells could not induce an elevation of circulating soluble forms of L-selectin in normal mice, as compared to lymphoma cells expressing L-selectin. Moreover, soluble forms of L-selectin were detected in the serum in mice bearing lymphoma induced by injection of T lymphoma cells expressing L-selectins. Interestingly, we also found that lymphoma cells that are unable to shed L-selectin in vitro following exposure to phorbol ester can generate soluble forms of serum L-selectin in vivo. Taken together, these results indicate that lymphoma cells are the major contributors to levels of soluble forms of L-selectins in lymphoma-bearing mice.