Modulation of human basophil histamine release by insulin-like growth factors.
Several lines of evidence indicate that basophils play an active pathogenic role in the late-phase reaction. Inasmuch as various cytokines are produced locally by activated cells of the immune system during late-phase reaction, "priming" of basophils by cytokines has become an area of active study over the last few years. We studied the effect of insulin-like growth factor (IGF)-I, shown to be active on immature and mature hemopoietic cells, on histamine release from human basophils. IGF-I enhanced histamine release initiated by anti-IgE, calcium ionophore A23187, and phorbol ester in a dose-dependent fashion (ED50: 300-600 pM), although IGF-I had little or no effect on the release caused by FMLP and C5a. The priming effect of IGF-I took place rapidly and reached plateau levels in 15 min. IGF-II and insulin, both of which have high amino acid sequence homology with IGF-I, also primed basophils. The order of enhancing potencies was IGF-I > IGF-II > insulin; IGF-I was 10-fold more potent than IGF-II and 250-fold more potent than insulin. Although specific receptors for each factor have been identified, blocking experiments using a mAb against IGF-I receptor showed almost complete abolishment of the enhancing effect of these factors, indicating that the enhancing effect is exhibited via the IGF-I receptor. Inasmuch as IGF-I has been shown to be produced by alveolar macrophages, fibroblasts, and nasal polyps, these results indicate that IGF may regulate allergic reactions in vivo by enhancing histamine release from basophils.
Hirai
K
K
Department of Medicine and Physical Therapy, University of Tokyo, School of Medicine, Japan.
Miyamasu
M
M
Yamaguchi
M
M
Nakajima
K
K
Ohtoshi
T
T
Koshino
T
T
Takaishi
T
T
Morita
Y
Y
Ito
K
K
D001491:Basophils / Q000502:physiology*; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D017455:Receptors, IgE / Q000502:physiology; D017451:Receptors, Somatomedin / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013189:SRS-A / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects
D007328:Insulin; D017455:Receptors, IgE; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013189:SRS-A; D007073:Immunoglobulin E; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II