Expression and regulation of monocyte chemoattractant protein-1 by human eosinophils.
Several recent studies have identified eosinophils as a cellular source of various cytokines, indicating that eosinophils play not only an effector role, but also a regulatory role within the allergic inflammatory cell network. In this study, we demonstrate that eosinophils can generate and secrete monocyte chemoattractant protein-1 (MCP-1), a prototype of C-C chemokines. Eosinophils generated immunoreactive MCP-1 in response to such diverse stimuli as C5a, formyl-methionyl-leucyl-phenylalanine (FMLP) and ionomycin, but MCP-1 production was not induced by interleukin (IL)-1 or tumor necrosis factor-alpha. C5a- and FMLP-induced eosinophil MCP-1 production was absolutely dependent on pretreatment with cytochalasin B. Eosinophils elaborated significantly more MCP-1 than neutrophils. Immunoreactive MCP-1 was detected at 6 h of incubation with C5a or FMLP. Expression of MCP-1 mRNA reached a maximum within the first 3 h after stimulation and then declined rapidly to a very low and stable level by 18 h. Pretreatment with IL-5 markedly amplified C5a-induced MCP-1 production, and the enhancement occurred at the pretranslational level. Eosinophil-active chemokines such as eotaxin failed to induce MCP-1 generation, even when eosinophils were primed by IL-5. Since MCP-1 exerts a potent histamine-releasing effect on human basophils, our results indicate that eosinophils may regulate basophil mediator release with possible consequent contribution to the pathogenesis of allergic inflammation via a paracrine mechanism.
Izumi
S
S
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
Hirai
K
K
Miyamasu
M
M
Takahashi
Y
Y
Misaki
Y
Y
Takaishi
T
T
Morita
Y
Y
Matsushima
K
K
Ida
N
N
Nakamura
H
H
Kasahara
T
T
Ito
K
K
D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000494:pharmacology; D015936:Complement C5a / Q000819:agonists / Q000494:pharmacology; D004804:Eosinophils / Q000737:chemistry / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015848:Interleukin-5 / Q000819:agonists / Q000494:pharmacology; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis
D018932:Chemokine CCL2; D018925:Chemokines; D015848:Interleukin-5; D012333:RNA, Messenger; D015936:Complement C5a