Interleukin-4 induces homotypic aggregation of human mast cells by promoting LFA-1/ICAM-1 adhesion molecules.
We report here that interleukin-4 (IL-4) induces homotypic aggregation of cultured human mast cells, grown from cord blood mononuclear cells in the presence of stem cell factor and IL-6. This aggregation was specifically induced by IL-4, because other cytokines including IL-1alpha, IL-1beta, IL-2, IL-3, IL-5, IL-9, IL-10, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor, NGF-beta, and tumor necrosis factor-alpha failed to show such effect. Flow cytometric analysis of the cultured mast cells showed that IL-4 increases the expression of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), but not of very late antigen (VLA) family adhesion molecules or vascular cell adhesion molecule-1 (VCAM-1). Neutralizing monoclonal antibodies specific for LFA-1alpha, LFA-1beta, or ICAM-1 inhibited the IL-4-induced homotypic aggregation of the mast cells, indicating that the aggregation was mediated mainly by LFA-1/ICAM-1 interaction. In addition, IL-4-treated but not untreated mast cells bound to immobilized ICAM-1. This binding was also inhibited by anti-LFA-1 or anti-ICAM-1. These results show that IL-4 promotes expression of ICAM-1 and LFA-1 molecules on mast cells, and suggest that IL-4 may contribute to the migration of mast cells into the inflamed tissue and to the cellular interaction with other inflammatory cells by upregulating adhesion molecules.
Toru
H
H
Department of Pediatrics, School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
Kinashi
T
T
Ra
C
C
Nonoyama
S
S
Yata
J
J
Nakahata
T
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018914:Cells, Immobilized; D016207:Cytokines / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D007700:Kinetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis* / Q000502:physiology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007378:Interleukins; D016169:Lymphocyte Function-Associated Antigen-1; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor