Absence of functional inhibition of cloned human β2‐adrenergic receptors by autoantibodies in asthmatic subjects

Abstract

Using guinea-pig lung membranes and cloned human beta 2-receptor adrenergic receptors the effects of whole serum, plasma, purified immunoglobulins and cellular activation products on beta 2-adrenergic receptor ligand binding and function were investigated. Sera from 24 non-asthmatic subjects and 115 asthmatics in different clinical categories were studied. There were no significant differences between antagonist ([125I] cyanopindolol) inhibition mediated by serum, plasma or by purified IgG when the asthmatics were compared with non-asthmatics. There was also no inhibition of 10(-6) M isoproterenol stimulated cAMP release from L cells expressing human beta 2-adrenergic receptors, by plasma, DEAE purified IgG fractions from asthmatics and non-asthmatics, or by products of activated platelets or lymphocytes. Since we have no evidence that immunoglobulins from asthmatic subjects exert functional inhibition of human beta 2-adrenergic receptors we conclude that autoantibodies to the beta 2-adrenergic receptors do not play an important functional role in the pathophysiology of asthma.