Stimulation of monocyte cGMP by leukocyte dialysates

from leukocyte lysates containing dialyzable transfer factor activity and other leukocyte dialysates devoid of transfer factor activity on accumulation of cyclic nu-cleotides in human leukocytes. Dialysates from normal leukocytes produced 4- to 11-fold increases in leukocyte cGMP, and experiments with purified cell populations revealed that the increases were predominantly, if not entirely, in blood monocytes. Substances that increased monocyte cGMP could be obtained from several cell populations including mononuclear cells from Hypaque-Ficoll gradients, plastic-adherent monocytes, nonad-herent lymphocytes, and neutrophils, but were not pres-ent in dialysates of leukemic lymphocytes from patients with the Sezary syndrome. Moreover, dialysates that increased leukocyte cGMP had essentially no effect on intracellular cAMP. Dialysates of lysed mononuclear cells contained seroto-nin, ascorbate, and an unidentified cholinergic activity, agents known to increase leukocyte cGMP. After pas-sage of dialyzable transfer factor from mononuclear cells through a gel-filtration column, four fractions were obtained that increased leukocyte cGMP. Two of these fractions contained ascorbate; two other active fractions, including one that also caused conversion of delayed skin tests, did not contain detectable ascorbate or sero-tonin. The dialysate of lysed neutrophils also increased cGMP, but this activity was limited to the column frac-tions which contained ascorbic acid. These observations raise the possibility that alterations in monocyte cGMP content could modulate either the Received for publication 7 February 1975 and in revised form 12 June 1975. specific antigen-dependent, or, more likely, the antigen-independent activities in preparations of transfer factor