title: Immunopharmacology of anaphylatoxin-induced bronchoconstrictor responses.
abstract: The complement anaphylatoxin peptides, C3a and C5a, are potential mediators of immediate hypersensitivity reactions, eliciting many of the same actions on isolated tissue and cell preparations as specific antigen. Instilled intratracheally in experimental animals, the peptides induce acute bronchospasms and are sometimes lethal. In vitro, they cause dose-dependent contraction of isolated lung tissue preparations, a response which correlates well with bronchospasms observed in vivo, and our current understanding of the cellular and molecular mechanisms of this action are reviewed here. C5a and its catabolic derivative, C5ades Arg, stimulate contraction of isolated guinea pig lung parenchymal strips in part by production of leukotrienes that constitute SRS-A, and by release of histamine. Leukotrienes in turn release thromboxane from lung tissue, and evidence indicates that at least part of the spasmogenic activity of these peptidolipids is mediated by this effect. C3a is considerably less potent than C5a in contracting lung tissues and appears to act primarily by causing the release of spasmogenic cyclooxygenase metabolites. Both peptides may additionally have direct action on contractile cells within the tissue. Platelet-activating factor (PAF), an unusual phospholipid mediator released from inflammatory cells stimulated with C5a and other agents, also contracts isolated lung parenchymal tissues. PAF stimulates release of significant quantities of thromboxane from guinea pig lung; however, indomethacin does not block contractile responses of the tissue. Recent evidence indicates that PAF may act on parasympathetic neurons in lung to release endogenous acetylcholine, and this action may be a major component of tissue responses to this mediator. Thus the complement anaphylatoxins stimulate release of many of the same mediators from lung tissues as are released by antigen challenge of sensitized tissue, and may, therefore, play an important role in the pathogenesis of allergic bronchospasms.
mesh_terms: D000706:Anaphylatoxins / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D001986:Bronchial Spasm / Q000276:immunology; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology / Q000494:pharmacology; D015926:Complement C3a; D003182:Complement C5 / Q000276:immunology / Q000494:pharmacology; D015936:Complement C5a; D004305:Dose-Response Relationship, Drug; D007249:Inflammation; D007975:Leukotriene B4 / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010455:Peptides / Q000276:immunology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology
chemical_list: D000706:Anaphylatoxins; D003176:Complement C3; D003182:Complement C5; D010455:Peptides; D010972:Platelet Activating Factor; D013189:SRS-A; D007975:Leukotriene B4; D015926:Complement C3a; D015936:Complement C5a