Stimulus specific of matrix metalloproteinase dependence of human T cell migration through a model basement membrane

Department of Medicine, University of California Medical Center, San Francisco 94143-0711, USA.
The Journal of Immunology (Impact Factor: 4.92). 02/1996; 156(1):160-7.
Source: PubMed


Chemotaxis of human T lymphoblastoma cells of the Tsup-1 line, which migrate similarly to blood T cells, through a layer of basement membrane-like Matrigel on a polycarbonate micropore filter was evoked by vasoactive intestinal peptide (VIP; concentration for a maximal response, 10(-7)M), IL-2 (10(-9)M), and the chemokines RANTES (10(-10)M) and macrophage inflammatory protein-1 alpha (10(-10)M). Chemotactic concentrations of each factor increased Tsup-1 cell secretion of matrix metalloproteinase-9 (MMP-9), with significant responses by 4 h for VIP, IL-2, and IL-4, but only after 24 h for macrophage inflammatory protein-1 alpha and RANTES, as quantified by Western blots and zymography. 3H-Labeled type IV human collagen incorporated in the Matrigel layer was degraded by migrating Tsup-1 cells, as assessed by release of radioactive fragments of the collagen. The in situ degradation of type IV collagen in Matrigel by migrating Tsup-1 cells was enhanced most significantly by VIP, IL-2, and IL-4 after 4 h at concentrations that increased the secretion of MMP-9 optimally, but only after 24 h by macrophage inflammatory protein-1 alpha and RANTES. The specific MMP inhibitor GM6001 suppressed Tsup-1 cell MMP activity evoked by all stimuli, as determined by zymography and in situ degradation of 3H-Labeled type IV human collagen. The chemotactic migration of Tsup-1 cells through Matrigel, but not through a filter alone, in response to optimal concentrations of VIP, IL-2, and IL-4, but not the chemokines, was inhibited by GM6001, with a concentration dependence similar to that for suppression of MMP activity. Thus elicitation of T cell chemotactic migration through a model basement membrane by stimuli that increase MMP activity early in the response depends on degradation of matrix proteins by MMP, whereas stimuli that recruit MMP late may rely on early activation of other proteases.

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    • "The rat NK cell line RNK-16 has also been used to study the role of MMPs in NK cell migration and both GM6001 and BB94 inhibited their migration through Matrigel by approximately 50% [9, 44]. Likewise, invasion through Matrigel by T cells (both freshly isolated and cell lines) is facilitated by MMPs, since treatment with GM6001 or BB94 can reduce invasion by 30%–70% [14, 23, 24, 45]. Migration of T cells may also be reduced using selective gelatinase inhibitors in experimental models of inflammation [29]. "
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    ABSTRACT: To efficiently combat solid tumours, endogenously or adoptively transferred cytotoxic T cells and natural killer (NK) cells, need to leave the vasculature, traverse the interstitium and ultimately infiltrate the tumour mass. During this locomotion and migration in the three dimensional environment many obstacles need to be overcome, one of which is the possible impediment of the extracellular matrix. The first and obvious one is the sub-endothelial basement membrane but the infiltrating cells will also meet other, both loose and tight, matrix structures that need to be overridden. Matrix metalloproteinases (MMPs) are believed to be one of the most important endoprotease families, with more than 25 members, which together have function on all known matrix components. This review summarizes what is known on synthesis, expression patterns and regulation of MMPs in cytotoxic lymphocytes and their possible role in the process of tumour infiltration. We also discuss different functions of MMPs as well as the possible use of other lymphocyte proteases for matrix degradation.
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    • "attention so far has focused on MMP-2 and -9, enzymes capable of degrading basement-membrane type IV collagen (Murphy et al, 1982, 1991; Hauzenberger et al, 1999; Amano et al, 2001). T cells can produce these two enzymes and the proposed role of both in the collagen degradation required for cell migration has been supported by in vitro experiments (Leppert et al, 1995; Menhang et al, 1996; Esparza et al, 1999). Normal and certain malignant B-cell types can also produce MMP-9 (Stetler- Stevenson et al, 1997; Girolamo et al, 1998; Trocme et al, 1998; Gaudin et al, 2000; Vacca et al, 2000) and sometimes also MMP-2 (Vacca et al, 2000). "
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    • "The recruitment of leukocytes into a site of tissue damage depends on their activation by cytokines and mobility through the endothelial barrier and the extracellular matrix with contemporary expression of adhesion molecules and matrix-degrading enzymes such as matrix metalloproteinase (MMPs) [6]. The aim of this work was to quantify the effects of oxidation in orthopedic UHMWPE on PBMCs viability and MMPs release in order to clarify the tissue response to oxidized polymeric biomaterial. "
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