Involvement of the spleen in the endotoxin-induced deterioration of the respiratory airway and lymphocyte β-adrenergic systems of the guinea pig

The β-adrenergic binding sites on splenic lymphocyte membranes of the guinea pig were characterized with the radio-ligand [125I]cyanopindolol and showed a maximal number of binding sites (B(max)) of 125 fmol/mg protein and an affinity (K(d)) of 170 pM. The potency of various β-adrenoceptor antagonists to compete for [125I]cyanopindolol binding suggested that the receptor is of the β2subtype. Endotoxin (1 mg/kg) induced a 35% decrease in the number of β-adrenergic binding sites on lymphocytes, 4 days after i.p. administration. The reduction in the number of β-adrenoceptors on the lymphocytes was accompanied by a 30% decrease in the relaxation of isolated guinea pig tracheal spirals to isoprenaline and a 20% reduction in the number of β-adrenergic binding sites in peripheral lung tissue. The endotoxin-induced deterioration of the β-adrenergic system in the respiratory airways was completely prevented by splenectomy. It is concluded that the spleen, and or cells or products derived from the spleen, are involved in the changes of the β-adrenergic system in the respiratory airways and lymphocytes.