Epinephrine promotes pulmonary angiitis: evidence for a beta1-adrenoreceptor-mediated mechanism.
Epinephrine (Epi) increases lymphocyte traffic to lung. We investigated whether Epi also modulates pulmonary cell-mediated immune responses in vivo. C57BL/6 mice were immunized with hen-egg lysozyme (HEL) on day 0, challenged with HEL intratracheally at day 12, and killed at day 15. Mice received Epi (0.5 mg/kg) subcutaneously during the sensitization phase, days 1-7 (Epi-SP), or the effector phase, days 12-14 (Epi-EP); controls received saline subcutaneously. Epi-SP mice showed increased airway inflammation (P < 0.03) and pulmonary angiitis (P < 0.04) characterized by endothelialitis and subendothelial fibrin deposition. Macrophages and granulocytes were increased in perivascular cuffs in situ (P < 0.001). CD3+ lymphocytes increased in the bronchoalveolar lavage fluid, whereas NK1.1+ and CD4+CD25+ lymphocytes decreased (all P < 0.05). Atenolol, a selective beta1-adrenoreceptor (AR) antagonist, inhibited the increased vascular and airway inflammation and the reduction in CD4+CD25+ lymphocytes (all P < 0.05) yielded by Epi, whereas all alpha/beta-AR blockers inhibited airway inflammation. We conclude that Epi-EP selectively promotes vascular inflammation in vivo via a beta1-receptor-mediated mechanism.
Immunopathology and Pulmonary and Critical Care Units, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Felipe A
FA
Jain
Long-Hai
LH
Zhao
Martin K
MK
Selig
Richard L
RL
Kradin
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D018925:Chemokines / Q000235:genetics; D003348:Cortisone / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000737:chemistry / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000276:immunology*; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D014657:Vasculitis / Q000139:chemically induced / Q000276:immunology*
D000318:Adrenergic beta-Agonists; D039481:CD11b Antigen; D018925:Chemokines; D018342:Receptors, Adrenergic, beta-1; D003348:Cortisone; D004837:Epinephrine