title: Trans-basement membrane migration of human basophils: role of matrix metalloproteinase-9.
abstract: In allergic disorders, basophils migrate from the blood stream to inflamed tissue sites. Since trans-basement membrane migration is an important step for local basophil accumulation, we performed a human basophil transmigration assay using a model basement membrane, Matrigel. IL-3 in the upper chamber was critical for basophil trans-basement membrane migration over baseline levels, since none of the chemoattractants placed in the lower chambers induced migration. RANTES, IL-8, 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) and platelet-activating factor (PAF) significantly up-regulated the transmigration of IL-3-treated basophils. Neutralizing experiments indicated the involvement of beta2 integrin and matrix metalloproteinase (MMP)-2/9 in basophil transmigration. Real-time quantitative PCR revealed that basophils constitutively expressed transcripts for MMP-9, and at lower levels, MMP-2, but cell-surface expression was only detected for MMP-9. MMP-9 was also detected in the cytoplasm and culture supernatant of the basophils. Treatment with IL-3 up-regulated the surface level of MMP-9 on the basophils. Our results suggest that basophils possess a unique regulatory mechanism for trans-basement membrane migration which is affected by cytokines, chemoattractants, beta2 integrin and MMPs, especially MMP-9. MMP-9 may be critically involved in the pathogenesis of local basophil influx in allergic diseases.
authors.affiliation: Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Tokyo 113-8655, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Suzukawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Komiya
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Iikura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagase
authors.forename: Chitose
authors.initials: C
authors.lastname: Yoshimura-Uchiyama
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Masao
authors.initials: M
authors.lastname: Yamaguchi
mesh_terms: D001485:Basement Membrane / Q000166:cytology* / Q000378:metabolism; D001491:Basophils / Q000502:physiology*; D001681:Biological Assay; D002465:Cell Movement / Q000276:immunology*; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D006801:Humans; D007797:Laminin / Q000737:chemistry; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D008954:Models, Biological; D011509:Proteoglycans / Q000737:chemistry
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D020780:Matrix Metalloproteinase 9