Inhibition of T cell adhesion to extracellular matrix glycoproteins by histamine: a role for mast cell degranulation products (original) (raw)
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Heterotypic adhesion-induced mast cell activation: biologic relevance in the inflammatory context
Molecular Immunology, 2002
In addition to being a major effector cell in the elicitation of allergic inflammation, mast cells have been found to be activated in various T cell-mediated inflammatory processes and to reside in close physical proximity to T cells. Such observations have led investigators to propose a functional relationship between these two cell populations. In this regard, we have recently reported that murine and human mast cells can be activated to both release granule-associated mediators, such as histamine and matrix metalloproteinase-9 (MMP-9), and to produce several cytokines (i.e. TNF-␣, IL-4 and IL-6) upon physical contact, which is adhesion molecule mediated, with activated T cells. This cascade of events, whereby mast cells are activated by T cells to release certain mediators which are known to be essential for leukocyte extravasation and recruitment to affected sites, points to an important immunoregulatory function of mast cells within the context of T cell-mediated inflammatory processes. : S 0 1 6 1 -5 8 9 0 ( 0 2 ) 0 0 0 8 9 -5
Fibronectin receptor integrins are involved in mast cell activation
Journal of Allergy and Clinical Immunology, 1994
Mast cells express fibronectin-receptor integrins on the cell surface, which are involved in cellular activation. In this study rat and mouse mast cells adhered to fibronectin through: very late antigen 4, 5 (ill integrin) and vitronectin receptor (~3 integrin), and engagement of these receptors promoted cellular degranulation induced by cross-linking of the high-affinity IgE receptor. Blocking of these adhesion molecules by monoclonal antibodies remarkably reduced passive cutaneous anaphylaxis reaction in vivo. On fibronectin, cytokine release from mast cells on IgE receptor aggregation was also enhanced, but not the expression of cytokine genes, with the exception of interleukin-3.
Previously, it was demonstrated that degranulation of RBL-2H3 mast cells is enhanced by α 5 β 1 integrin very late antigen-5 (VLA-5)-mediated adhesion to fibronectin. However, RBL-2H3 cells adhere nonspecifically to various substrates, and we therefore used mast cells cultured from mouse bone marrow (BMMC) to investigate the effect of adhesion to fibronectin on degranulation. It has been demonstrated previously that Mn 2+ induces a conformational change of VLA-5 into high-affinity for fibronectin. In our experiments, Mn 2+ -induced adhesion to fibronectin enhanced allergen-induced mast cell degranulation in vitro. Surprisingly, adhesion to fibronectin induced by Mn 2+ but also by Zn 2+ , Ni 2+ , and Co 2+ , metals that are known to induce contact hypersensitivity responses, directly triggered mast cell degranulation in vitro in absence of an antigenic stimulus. This effect could be blocked by soluble arginin-glycineaspartic acid (RGD) confirming a role for VLA-5. In addition, local injection of BMMC stimulated in vitro with Mn 2+ , into the skin of BALB/c mice resulted in spontaneous activation and enhanced allergen-induced activation of these cells in vivo. This response was also attenuated with soluble RGD peptide. In conclusion, our data show that VLA-5 can modulate mast cell sensitivity for antigenic stimulation and provide a plausible explanation for hypersensitivity responses to various metals in which cation-induced integrin-mediated adhesion directly triggers degranulation.
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2004
Background Mast cells exert profound pleiotropic effects on immune cell reactions at inflammatory sites, where they are most likely influenced not only by the extracellular matrix (ECM) and inflammatory mediators but also by the proximity of activated T lymphocytes. We recently reported that activated T cells induce mast cell degranulation with the release of TNF-a, and that this activation pathway is mediated by lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) binding. Objective To determine how this contact between the two cell types can modulate mast cell behaviour in an inflammatory milieu by examining the adhesion of mast cells to endothelial cells and ECM ligands in an integrin-dependent manner. Methods Human mast cells (HMC-1) were co-cultured with resting or activated T cells followed by testing their adhesion to endothelial cell and ECM ligands, stromal derived factor-1a (SDF-1a)induced migration, and western blotting. Results Co-culturing HMC-1 with activated, but not with resting T cells resulted in marked stimulation of mast cell adhesion to vascular cell adhesion molecule-1 and ICAM-1 in a very late antigen-4-and LFA-1-dependent fashion. In addition, activated T cells or T cell membranes promoted HMC-1 adhesion to fibronectin (FN) and laminin. This effect was accompanied by the phosphorylation of extracellular regulated kinase and p38, but not of c-Jun N-terminal kinase. Importantly, the adhesive property of mast cells depended exclusively on the direct contact between the two cell types, since neither supernatants from activated T cells nor separation of the two cell populations with a porous membrane affected mast cell adhesion to FN. Furthermore, similar results were obtained when mast cells were incubated with purified membranes from activated T cells. These results suggest that, in addition to stimulating mast cell degranulation, the proximity of activated T lymphocytes to mast cells can mediate the adhesion of mast cell precursors to the endothelial ligands and ECM. Activated T cells also stimulated SDF-1a-induced mast cell migration. Conclusion This symbiotic relationship between the two types of immune cells may serve to direct mast cells to specific sites of inflammation where their effector functions are required.
European Journal of Immunology, 2006
Histamine is released in inflammatory reactions and exerts an immunoregulatory function on cells present in the microenvironment. In this study, we compared the effect of histamine on degranulation of mast cells derived from animals bearing a parasitic infection with those from uninfected animals. Peritoneal mast cells (PMC) were obtained 24 days after infection of Wistar rats with Toxocara canis. The degree of degranulation was assessed either morphologically or by measuring the release of b-hexosaminidase and TNF-a. Non-purified PMC or mast cells immunomagnetically purified with mAb AA4 were used. An increase in degranulation of non-purified mast cells from infected animals was observed after incubation with histamine in vitro or when histamine was injected into the peritoneal cavity. When a purified mast cell population was used, this effect was no longer observed. Supernatants from spleen cells stimulated with histamine induced degranulation of purified mast cells, and again, this was potentiated with PMC from infected animals. However, when supernatants from peritoneal macrophages similarly stimulated were used, a reduction in the degranulation of PMC from infected animals was observed. Our results suggest that histamine may act as a regulator of mast cell degranulation, thus modulating inflammatory responses due to infection with certain parasites.
Journal of leukocyte biology, 1998
Activated mast cells reside in close apposition to T cells in some inflammatory processes. In this study, we analyzed whether this close physical proximity affects human mast cell degranulation and cytokine release. Thus HMC-1 human mast cells or primary bone marrow-derived human mast cells were cocultured with activated and with resting T cells. Mast cells cocultured with activated T cells released histamine and beta-hexosaminidase and produced tumor necrosis factor alpha (TNF-alpha), an effect that peaked at 20 h. Kinetics of histamine release paralleled the formation of heterotypic aggregates. Separation of the two cell populations with a porous membrane prevented mediator release and TNF-alpha production. Addition of the PI3-kinase inhibitor, wortmannin, inhibited the heterotypic adhesion-associated degranulation but not TNF-alpha production. These data thus indicate a novel pathway through which human mast cells are activated to both release granule-associated mediators and to ...
Clinical & Experimental Allergy, 1993
We have examined the possibility that mouse bone marrow-derived cultured mast cells (BMCMC) have the capacity to attach to and migrate on extracellular matrix components in vitro through the use of time lapse videography. Unactivated mast cells did not display significant interaction with slide flasks coated with either VA> BSA or collagen IV, and Fc,,RT-mediated activation of BMCMC did not appreciably increase their attachment and migratory characteristics. Both activated and unactivated BMCMC adhered to surfaces coated with a synthetic IKVAV laminin polypeptide, but this association resulted in the immobilization of the cells to the substrate. BMCMC did not adhere to surfaces coated with laminin, fibronectin or matrigel until Fc, Rl-mcdiated activation, after which they displayed rapid, random movement on these surfaces. Cells continually interacted with laminin, fibronectin or matrigel by flattening, interspaced by periods of movement as rounded cells with small pseudopodia. The mean velocity of BMCMC on laminin, fibronectin or matrigel was similar and averaged approximately 180 /im/hr. The mean velocity of BMCMC on these three substrates was not significantly different from the mean velocity of monocytes on laminin. The movement of BMCMC on these substrates demonstrated a directional tendency. In summary, these results demonstrate that mast cells activated through Fc,Rl are capable of attachment to and motion on components of extracellular matrix, and demonstrate one mechanism by which mast cells may migrate to areas of inflammation and wound repair.
Differential expression of integrin subunits on adherent and nonadherent mast cells
Brazilian Journal of Medical and Biological Research, 2003
Mast cell progenitors arise in bone marrow and then migrate to peripheral tissues where they mature. It is presumed that integrin receptors are involved in their migration and homing. In the present study, the expression of various integrin subunits was investigated in three systems of adherent and nonadherent mast cells. Mesentery mast cells, freshly isolated bone marrow-derived mast cells (BMMC) and RBL-2H3 cells grown attached to tissue culture flasks are all adherent mast cells and peritoneal mast cells, and cultured BMMC and RBL-2H3 cells grown in suspension represent nonadherent mast cell populations. Pure populations of mast cells were immunomagnetically isolated from bone marrow, mesentery and peritoneal lavage using the mast cell-specific monoclonal antibody AA4. By immunomicroscopy, we could demonstrate that all of these mast cells expressed α4, α5, α6, ß1 and ß7 integrin subunits. The expression of the α4 integrin subunit was 25% higher in freshly isolated mesentery mast cells and BMMC. Consistent with the results obtained by immunomicroscopy, mesentery mast cells expressed 65% more mRNA for the α4 integrin subunit than peritoneal mast cells. In vitro studies were also conducted using the rat mast cell line RBL-2H3. RBL-2H3 cells grown attached to the tissue culture flasks or as suspension cultures expressed the same integrin subunits identified in bone marrow, mesenteric and peritoneal mast cells ex vivo. Similarly, the expression of α4 integrin was higher in adherent cells. Therefore, α4 integrins may play a critical role in the anchorage of mast cells to the extracellular matrix in bone marrow and in peripheral tissues.
Mast Cell Degranulation and Histamine Release Observed in a New in Vitro System
Journal of Experimental Medicine, 1960
Mast cells participate in some types of inflammatory reactions involving changes in the microcirculation of certain tissues. Among the known vasoactive substances of importance, histamine has been found in mast cells (1) of several species of animals and in certain species serotonin is also present (2). A variety of substances (the formaldehyde polymer of p-methoxyphenethylmethylamine (48/80), ovomucoid, and dextran) when administered to the rat elicit an inflammatory response, cause histamine and serotonin release and the morphological change of degranulation . No clear description of the process involved in release of the active amines and other mast cell constituents has yet been presented. A major obstacle has been the lack of an appropriate way of observing the action of various agents on the structure of the mast cell and its constituents under controlled conditions. Hence, a new method of observation was sought to study the mechanism of mast cell secretion in vitro.