In vivo influences of phorbol ester and calcium ionophore on lymphocyte traffic, lymph flow and efferent lymph levels of thromboxane B2 in sheep.
In vitro systems have provided increasing evidence of significant lymphocyte transmembrane signalling by plasma membrane receptors which utilize antigen and other ligand activation of the inositol phosphate dual second messenger system of intracellular signalling. Elevation of intracellular Ca2+ and activation of protein kinase C are important products of these signals and appear to provide a complete set of mitogenic signals for both T and B cells. Calcium inophore and phorbol ester have been found to mimic these events in vitro and are here employed in vitro to study their effects on lymphocyte traffic and efferent lymph flow through primary peripheral lymph nodes of sheep and on the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. Calcium ionophore and phorbol ester were given alone or in combination to popliteal lymph nodes of sheep by drainage area injection or by acute infusion into cannulated afferent lympatics of study popliteal lymph nodes whose efferent lymphatic was chronically cannulated for study. The findings resembled those of drainage area immunization with an early increase in efferent lymph flow and prompt and marked depressions in the output into efferent lymph of both small recirculating and blast lymphocytes ('shutdown', 'recruitment'), followed by a marked increase in the output into efferent lymph of both small recirculating and blast lymphocytes. The greatest elevation in both small recirculating and blast lymphocyte outputs was at 24 and 48 h following phorbol ester and calcium ionophore administration. Acute phorbol ester and calcium ionophore administration was associated with a prompt and marked elevation in efferent lymph levels of thromboxane B2 which were of short duration. The findings observed here with lymph node drainage area infusion/injection of both phorbol ester and calcium ionophore are quite similar to those encountered in this sheep lymphocyte traffic model following popliteal lymph node drainage area immunization with killed Salmonella muenchen antigen.
Moore
T C
TC
Department of Surgery, UCLA School of Medicine, Torrance 90509.
Lami
J L
JL
Said
S I
SI
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D008196:Lymph / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects / Q000276:immunology; D012756:Sheep; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D000001:Calcimycin; D013929:Thromboxane B2; D013755:Tetradecanoylphorbol Acetate