Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells <i>in vivo</i>

He, Shaoheng; Walls, Andrew F.

doi:10.1038/sj.bjp.0702223

Cited by 137 publications

(104 citation statements)

References 57 publications

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“…As shown in Figure 5, dermal eosinophil number of chymase-injected mice was approximately 7.6-fold and 21-fold at 7 days after the first and fourth injection of chymase, respectively, as compared with that of the corresponding control. The result is consistent with the data of He and Walls (1998) who have shown that human chymase induces the accumulation of inflammatory cells including eosinophils in the peritoneal cavity of mice and the skin of guinea pigs.…”

Section: Effect Of Chymase Injection On Dermal Eosinophil Numbersupporting

confidence: 82%

Chymase Participates in Chronic Dermatitis by Inducing Eosinophil Infiltration

Tomimori

Muto

Fukami

et al. 2002

Laboratory Investigation

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SUMMARY:An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis. (Lab Invest 2002, 82:789 -794).A topic dermatitis (AD) is a chronic eczematous skin disorder characterized by dry and itchy skin. The patients with AD often have a family history of other allergic diseases including asthma and hay fever. Although AD is known to be a manifestation of immediate hypersensitivity mediated by IgE, delayed-type hypersensitivity is also involved in the skin reaction of the patients (Tanaka et al, 1994;Varela et al, 1999). Interestingly, in mice, repeated application of contact sensitizing agents, such as 2,4-dinitrofluorobenzene (DNFB) and trinitrochlorobenzene, develops an immediate-type reaction, in contrast to a single application that causes a typical delayed-type reaction (Kitagaki et al, 1995(Kitagaki et al, , 1997. Repeated elicitation with such agents not only increases the serum level of IgE but also induces Th2-type cytokine expression (Nagai et al, 1997b). In addition, mast cell accumulation occurs in the dermis because of the repeated challenge (Kitagaki et al, 1995), as is often observed in AD patients. Therefore, this animal model is thought to be valuable for studying human AD.Chymase is a chymotrypsin-like serine protease and is primarily stored in secretory granules of mast cells (Schwartz and Austen, 1980). Chymase cleaves a variety of physiological substances, including metalloproteases (Fang et al, 1997), procollagen (Kofford et al, 1997), precursor of interleukin 1␤ (IL-1␤) (Mizutani et al, 1991b), and membrane-associated stem cell factor (Longley et al, 1997), while its precise role is not clear. Human mast cells are classified into two types, MC TC and MC T , based on their composition of serine protease (Irani et al, 1986). MC TC contains both chymase and tryptase, while MC T expresses tryptase but not chymase. Because MC TC predominates in the skin (Irani et al, 1989), chymase has been implicated in the pathogenesis of skin disorders complic...

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Section: Effect Of Chymase Injection On Dermal Eosinophil Numbersupporting

confidence: 82%

Chymase Participates in Chronic Dermatitis by Inducing Eosinophil Infiltration

Tomimori

Muto

Fukami

et al. 2002

Laboratory Investigation

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“…Injection of human chymase or tryptase into guinea pig skin or mouse peritoneal cavity resulted in substantial neutrophil and eosinophil recruitment within 3 h (39,40). Injection of human chymase into mouse ear also resulted in polymorphonuclear cell recruitment (41,42).…”

Section: Discussionmentioning

confidence: 99%

Proteolytic Activation of Alternative CCR1 Ligands in Inflammation

Berahovich

Miao

Wang

et al. 2005

The Journal of Immunology

150

126

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Although chemokines CCL3/MIP-1α and CCL5/RANTES are considered to be primary CCR1 ligands in inflammatory responses, alternative CCR1 ligands have also been described. Indeed, four such chemokines, CCL6/C10/MIP-related protein-1, CCL9/MIP-1γ/MIP-related protein-2, CCL15/MIP-1δ/hemofiltrate CC chemokine-2/leukotactin-1, and CCL23/CKβ8/myeloid progenitor inhibitory factor-1, are unique in possessing a separately encoded N-terminal domain of 16–20 residues and two additional precisely positioned cysteines that form a third disulfide bridge. In vitro, these four chemokines are weak CCR1 agonists, but potency can be increased up to 1000-fold by engineered or expression-associated N-terminal truncations. We examined the ability of proinflammatory proteases, human cell supernatants, or physiological fluids to perform N-terminal truncations of these chemokines and thereby activate their functions. Remarkably, most of the proteases and fluids removed the N-terminal domains from all four chemokines, but were relatively unable to cleave the truncated forms further. The truncated chemokines exhibited up to 1000-fold increases in CCR1-mediated signaling and chemotaxis assays in vitro. In addition, N-terminally truncated CCL15/MIP-1δ and CCL23/CKβ8, but not CCL3/MIP-1α or CCL5/RANTES, were detected at relatively high levels in synovial fluids from rheumatoid arthritis patients. These data suggest that alternative CCR1 ligands are converted into potent chemoattractants by proteases released during inflammatory responses in vivo.

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“…Mast cells and eosinophils are both components of the innate arm of the CD4 ϩ Th2-mediated immune responses, and co-localize in many Th2-mediated inflammatory reactions that occur during allergy and parasitic infections. A number of mast cell-derived mediators has been shown to prime or activate eosinophil responses, whereas eosinophil-derived mediators can also directly affect mast cells responses (41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). In fact, mast celldeficient mice develop less eosinophilia than wild-type mice in models of allergic airways disease (AAD) (52).…”

Section: Discussionmentioning

confidence: 99%

Eotaxin Selectively Binds Heparin

Ellyard

Simson²,

Bezos

et al. 2007

Journal of Biological Chemistry

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An important feature of chemokines is their ability to bind to the glycosaminoglycan (GAG) side chains of proteoglycans, predominately heparin and heparan sulfate. To date, all chemokines tested bind to immobilized heparin in vitro, as well as cell surface heparan sulfate in vitro and in vivo. These interactions play an important role in modulating the action of chemokines by facilitating the formation of stable chemokine gradients within the vascular endothelium and directing leukocyte migration, by protecting chemokines from proteolysis, by inducing chemokine oligomerization, and by facilitating transcytosis. Despite the importance of eotaxin in eosinophil differentiation and recruitment being well established, little is known about the interaction between eotaxin and GAGs and the functional consequences of such an interaction. Here we report that eotaxin binds selectively to immobilized heparin with high affinity (K d ‫؍‬ 1.23 ؋ 10 ؊8 M), but not to heparan sulfate or a range of other GAGs. The interaction of eotaxin with heparin does not promote eotaxin oligomerization but protects eotaxin from proteolysis directly by plasmin and indirectly by cathepsin G and elastase. In vivo, co-administration of eotaxin and heparin is able to significantly enhance eotaxin-mediated eosinophil recruitment in a mouse air-pouch model. Furthermore, when heparin is coadministered with eotaxin at a concentration that does not normally result in eosinophil infiltration, eosinophil recruitment occurs. In contrast, heparin does not enhance eotaxin-mediated eosinophil chemotaxis in vitro, suggesting protease protection or haptotactic gradient formation as the mechanism by which heparin enhances eotaxin action in vivo. These results suggest a role for mast cell-derived heparin in the recruitment of eosinophils, reinforcing Th2 polarization of inflammatory responses.Chemokines are a superfamily of proteins that control the migration of leukocytes to sites of inflammation during an immune response. A feature of chemokines is their ability to bind to the glycosaminoglycan (GAG) 3 side chains of proteoglycans, predominately heparin and heparan sulfate. To date, all chemokines tested bind to immobilized heparin in vitro, as well as cell surface heparan sulfate in vitro and in vivo (1). In vitro, chemokine-heparin or heparan sulfate binding may be competitively inhibited by the GAGs chondroitin sulfate and dermatan sulfate (1, 2), suggesting that some chemokines may also bind these GAGs. Different chemokines bind heparin or heparan sulfate with varying affinity (1-3), and four different models, or docking modes, have been proposed for the interaction of chemokines with heparin and heparan sulfate (4). Heparin and heparan sulfate play an important role in modulating the function of chemokines (5) and have been proposed to control chemokine action in three ways. First, it is well established that heparan sulfate immobilizes chemokines on the luminal surface of endothelial cells (6, 7), which is essential for the formation of stable chemokine...

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Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo

Cited by 137 publications

References 57 publications

Chymase Participates in Chronic Dermatitis by Inducing Eosinophil Infiltration

Chymase Participates in Chronic Dermatitis by Inducing Eosinophil Infiltration

Proteolytic Activation of Alternative CCR1 Ligands in Inflammation

Eotaxin Selectively Binds Heparin

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