Cholinergic enhancement of megakaryocytopoiesis and granulocytopoiesis in culture: mediation via T-lymphocytes.

Addition of carbamylcholine, a cholinergic analogue, to bone marrow cultures enhanced megakaryocytic and granulocytic growth by 60% and 42%, respectively. When carbamylcholine was added to spleen cells cultured in the presence of pokeweed mitogen, the resulting conditioned medium (PWM-SCM) increased the number of megakaryocytic and granulocytic colonies to 159% +/- 6% and 146% +/- 10%, respectively, compared to control cultures stimulated by PWM-SCM alone. To determine if this cholinergic augmentation of colony formation was direct or mediated via accessory marrow cells, cyclosporin A (CyA), a potent T-lymphocyte function inhibitor known to suppress the production of colony-stimulating activity (CSA) by spleen cell cultures, was added to marrow cultures. CyA (3 micrograms/ml) abrogated the enhancement of megakaryocytic and granulocyte-macrophage colony growth but had no effect on colony formation when added alone. To confirm the role of T-lymphocytes in the augmented proliferation of megakaryocytopoiesis and granulocytopoiesis, bone marrow cells from T-lymphocyte-deficient nude mice were cultured in the presence of carbamylcholine. No significant change was observed in the number of megakaryocyte colony-forming units (CFU-M) and committed granulocyte-macrophage colony-forming units (CFU-C) derived from the marrow of nude mice when cultured in the presence of carbamylcholine. The data suggest that carbamylcholine-induced enhancement of megakaryocytopoiesis and granulocytopoiesis in culture is indirect, requiring a T-lymphocyte population.