Depression of neutrophil chemotaxis in atopic individuals. An H2 histamine receptor response.
Neutrophil chemotaxis was compared in normal and atopic individuals using a modified Boyden chamber with as chemotactant, autologous serum either unactivated or activated by zymosan or an endotoxin-containing house dust preparation. A high incidence of defective leukotaxis was found in atopics when cells were opposed to activated serum. The cause of this abnormality is not intrinsic to the leukocytes since random migration and chemotaxis towards unactivated serum were comparable in normal and atopic subjects. The defect persisted when atopic leukocytes were opposed to activated normal serum and the chemotactic response of normal neutrophils was not imparied when tested against activated atopic serum. Leukotaxis was significantly depressed by incubating atopic leukocytes with allergen to which they were sensitized, suggesting an inhibitory effect of mediators of anaphylaxis. Histamine inhibited in vitro neutrophil chemotaxis in normal and atopic subjects. This inhibition was dose-related and significantly more pronounced in atopics. Incubation of atopic leukocytes with an H2 antagonist, cimetidine, was capable of enhancing their chemotactic responsiveness towards activated autologous serum to levels observed in normal controls. In the same conditions, an H1 blocker, promethazine, was without effect. These data indicate that the leukotactic dysfunction of atopic individuals results from an abnormal sensitivity of these leukocytes to histamine which, in the chemotactic chamber, may be released from basophils by products of complement activation and, in some experimental conditions, by antigen to which cells are sensitized.
D002634:Chemotaxis, Leukocyte; D002927:Cimetidine / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004391:Dust; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D008297:Male; D009504:Neutrophils; D011398:Promethazine / Q000494:pharmacology; D011968:Receptors, Histamine / Q000276:immunology*; D011970:Receptors, Histamine H2 / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
D004391:Dust; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D002927:Cimetidine; D015054:Zymosan; D011398:Promethazine