Induction of functional IL-8 receptors by IL-4 and IL-13 in human monocytes.
IL-8 and related Glu-Leu-Arg (ELR+) CXC chemokines are potent chemoattractants for neutrophils but not for monocytes. IL-13 and IL-4 strongly increased CXCR1 and CXCR2 chemokine receptor expression in human monocytes, macrophages, and dendritic cells. The effect was receptor- and cell type-selective, in that CCRs were not increased and no augmentation was seen in neutrophils. The effect was rapid, starting at 4 h, and concentration dependent (EC50 = 6.2 and 8.3 ng/ml for CXCR1 and CXCR2, respectively) and caused by new transcriptional activity. IL-13/IL-4-treated monocytes showed increased CXCR1 and CXCR2 membrane expression. IL-8 and related ELR+ chemokines were potent and effective chemotactic agents for IL-13/IL-4-treated monocytes, but not for untreated mononuclear phagocytes, with activity comparable to that of reference monocyte attractants, such as MCP-1. In the same cells, IL-8 also caused superoxide release. Macrophages and dendritic cells present in biopsies from Omenn's syndrome and atopic dermatitis patients, two Th2 skewed pathologies, expressed IL-8 receptors by immunohistochemistry. These results show that IL-13 and IL-4 convert IL-8 and related ELR+ chemokines, prototypic neutrophil attractants, into monocyte chemotactic agonists, by up-regulating receptor expression. Therefore, IL-8 and related chemokines may contribute to the accumulation and positioning of mononuclear phagocytes in Th2-dominated responses.
Bonecchi
R
R
Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
Facchetti
F
F
Dusi
S
S
Luini
W
W
Lissandrini
D
D
Simmelink
M
M
Locati
M
M
Bernasconi
S
S
Allavena
P
P
Brandt
E
E
Rossi
F
F
Mantovani
A
A
Sozzani
S
S
D015703:Antigens, CD / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D015152:Blotting, Northern; D002634:Chemotaxis, Leukocyte; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D016897:Respiratory Burst / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D005609:Free Radicals; D018793:Interleukin-13; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D015847:Interleukin-4