title: Elevated intracellular cyclic AMP inhibits chemotaxis in human eosinophils.
abstract: Elevated intracellular cyclic AMP is associated with the inhibition of many inflammatory cellular responses. In this study, we examined the effect of cyclic AMP on eosinophil chemotaxis. Eosinophils were isolated from healthy human volunteers using an immunomagnetic method. Eosinophils were treated with agents that elevate intracellular cyclic AMP and evaluated for chemotactic responses to platelet-activating factor (PAF; 10(-6) M) and to complement factor 5a (C5a; 10(-8) M) in microchemotaxis chambers. Forskolin, prostaglandin E1 (PGE1), and a phosphodiesterase (PDE) IV-selective inhibitor inhibited eosinophil chemotactic responses. The mean per cent inhibition of eosinophil chemotaxis in response to PAF by forskolin, PGE1, and the PDE IV-selective inhibitor (10(-5) M) was 16.8 +/- 5.3, 26.6 +/- 9.5, and 35.1 +/- 6.1%, respectively (n = 5). The corresponding values for C5a were 17.5 +/- 7.9, 20.8 +/- 10.7, and 39.5 +/- 5.0%. An exogenous cyclic AMP analogue (dibutyryl cyclic AMP, 10(-3) M) also inhibited eosinophil chemotaxis by 69.4 +/- 12.8 and 66.9 +/- 11.6% in response to PAF and C5a, respectively (n = 5). We conclude that elevated intracellular cyclic AMP inhibits eosinophil chemotaxis.
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco 94143-0130, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
authors.forename: R
authors.initials: R
authors.lastname: Alvarez
authors.forename: I F
authors.initials: IF
authors.lastname: Ueki
authors.forename: J A
authors.initials: JA
authors.lastname: Nadel
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D015936:Complement C5a / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology
chemical_list: D010726:Phosphodiesterase Inhibitors; D010972:Platelet Activating Factor; D011799:Quinazolines; C096328:RS 25344; D005576:Colforsin; D015936:Complement C5a; D000242:Cyclic AMP; D000527:Alprostadil