title: Differential response of human basophils and mast cells to recombinant chemokines.
abstract: Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 micrograms/ml: 26.9 +/- 3.4%; other chemokines: < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 microgram/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n = 2), skin (n = 1), uterus (n = 3), or tonsils (n = 3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2R beta, CD63, IL-3R alpha, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.
authors.affiliation: Department of Internal Medicine I, University of Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Füreder
authors.forename: H
authors.initials: H
authors.lastname: Agis
authors.forename: H
authors.initials: H
authors.lastname: Semper
authors.forename: F
authors.initials: F
authors.lastname: Keil
authors.forename: U
authors.initials: U
authors.lastname: Maier
authors.forename: M R
authors.initials: MR
authors.lastname: Müller
authors.forename: K
authors.initials: K
authors.lastname: Czerwenka
authors.forename: H
authors.initials: H
authors.lastname: Höfler
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: P
authors.initials: P
authors.lastname: Valent
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D000954:Antigens, Surface / Q000187:drug effects; D001491:Basophils / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D016207:Cytokines; D011994:Recombinant Proteins