Trans-basement membrane migration of human basophils: role of matrix metalloproteinase-9.
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.
Suzukawa
Maho
M
Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Tokyo 113-8655, Japan.
Komiya
Akiko
A
Iikura
Motoyasu
M
Nagase
Hiroyuki
H
Yoshimura-Uchiyama
Chitose
C
Yamada
Hirokazu
H
Kawasaki
Hiroshi
H
Ohta
Ken
K
Matsushima
Kouji
K
Hirai
Koichi
K
Yamamoto
Kazuhiko
K
Yamaguchi
Masao
M
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
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D020780:Matrix Metalloproteinase 9