Beta-adrenergic blockade: augmentation of neutrophil-mediated inflammation.
beta-Adrenergic blockade has been clinically associated with vascular occlusion. Because neutrophil activation, either alone or in concert with other blood cells, can induce vaso-occlusion by aggregation, leukoembolization, and inflammatory damage to vascular endothelium, we studied the effect of beta-adrenergic blockade on neutrophil activation in vitro and on microvascular integrity in vivo. beta-Adrenergic antagonists, propranolol and alprenolol, could induce dose-related and stereospecific activation of human neutrophils resulting in granulocyte aggregation and migration. Propranolol produced de novo aggregation and also enhanced responses to chemotaxins, N-formyl-methionyl-leucyl-phenylalanine and C5a. Lysosomal exocytosis was unaffected by beta blockers. In partial explanation of the enhancement of granulocyte activation by beta blockade, we observed that propranolol produced enhanced expression and affinity of granulocyte surface receptors for tritiated N-formyl-methionyl-leucyl-phenylalanine. This enhanced activation of human granulocytes by beta blockers was manifest in vivo as augmented inflammatory dermal edema. Enhanced granulocyte activation by beta blockade may induce microvascular disruption and subsequent tissue inflammation.
D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000473:pathology; D008247:Lysosomes / Q000201:enzymology; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000526:Alprenolol; D011433:Propranolol; D009113:Muramidase; D005966:Glucuronidase