Albumin exchange and inflammatory cell recruitment in lungs of antigen-challenged guinea pigs: role of histamine.
Microvascular albumin exchange and sequestration of inflammatory cells into the lungs of anesthetized guinea pigs immunized to ovalbumin were evaluated using radioactive tracers. Increased exchange of radiolabeled (*) albumin from airways to blood was noted in immunized and boosted animals under basal conditions. After the intratracheal injection of 300 micrograms of ovalbumin, an additional increase in exchange through epithelium occurred, since the rate of appearance of *albumin in blood was enhanced compared with control (140 +/- 30 vs. 54 +/- 20% in 1 h). The augmentation of lung content in extravascular *albumin compared with control (16.2 +/- 4.0 vs. 5.9 +/- 1.6%) indicates that transendothelial exchange was also facilitated. Concomitment with the sequestration of *platelets into the lungs of antigen-challenged sensitized animals (59.2 +/- 20% in 1 h), leukocytes (> 60% polymorphonuclear neutrophils) did not marginate. Histamine released during antigenic shock might promote leukocyte demargination from the vascular bed through its vasomotor effect and/or by inhibiting leukocyte activation and consequently may counteract the effects of other inflammatory mediators acting to sequester neutrophils. In confirmation, perfusion of histamine to the immunized animals induced demargination of lung leukocytes. Histamine antagonists prevented the increased exchange of *albumin through the epithelial and endothelial barriers and uncovered *leukocyte sequestration (100.7 +/- 28.9% in 1 h) in the lungs of antigen-challenged animals. Histamine antagonists may favor antigen-induced leukocyte sequestration in the lungs by preventing the effects of endogenous histamine on capillary recruitment and blood flow.
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-Institut National de la Santé et de la Recherche Médicale 285, Paris, France.
M F
MF
Bureau
C D
CD
Arreto
J
J
Lefort
B B
BB
Vargaftig
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001792:Blood Platelets / Q000502:physiology; D001810:Blood Volume / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004912:Erythrocytes / Q000502:physiology; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007249:Inflammation / Q000097:blood / Q000473:pathology*; D007962:Leukocytes / Q000502:physiology; D008168:Lung / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology*; D013670:Sodium Pertechnetate Tc 99m
D000941:Antigens; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D006632:Histamine; D010047:Ovalbumin; D013670:Sodium Pertechnetate Tc 99m