Integrin-dependent role of human T cell matrix metalloproteinase activity in chemotaxis through a model basement membrane
✍ Scribed by Menghang Xia; Sunil P. Sreedharan; Paul Dazin; Caroline H. Damsky; Edward J. Goetzl
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 644 KB
- Volume
- 61
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Human T lymphoblastoma cells of the CD4+ 8+ Tsup-1 line, that express alpha4 and alpha5 but not alpha6 integrins of the betal family, and CD4+ human blood T cells bind vasoactive intestinal peptide (VIP) with high affinity, leading to increased adherence, secretion of matrix metalloproteinases (MMPs), and chemotaxis. VIP-enhanced adherence of T cells to fibronectin was inhibited significantly by neutralizing monoclonal antibodies to betal > alpha4 >> alphas, but not to alpha6. Antibodies to betal and alpha4 suppressed to a similarly significant extent VIP stimulation of both MMP-dependent T cell chemotaxis through fibronectin-enriched Matrigel and T cell degradation of 3H-type IV collagen in the Matrigel, without affecting VIP-evoked secretion of MMP by suspensions of T cells. The lesser inhibition of VIP-enhanced adherence of T cells to fibronectin by anti-alpha5 antibody, than antibodies to betal or alpha4 chains, was associated with lesser or no suppression of MMP-dependent T cell chemotaxis through Matrigel and T cell degradation of type IV collagen in the Matrigel in response to VIP. Specific betal integrins thus mediate interactions of stimulated T cells with basement membranes, including adherence, localized digestion by MMPs, and chemotactic passage, that promote entry of T cells into extravascular tissues.