Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous investigations in our laboratory have shown that mast cells play a significant role in the initiation of immune complex-mediated inflammation. Histamine, leukotrienes, and TNF released from mast cells are important mediators of early inflammatory processes. In the peritoneal reverse passive Arthus reaction, we observed a biphasic release of TNF. Mast cells were responsible for the first peak. The complement system is also known to be central to the expression of antibody-induced immune injury. Therefore, in this study, we investigated the significance of activated complement in regulating mast cell stimulation and neutrophil recruitment in the peritoneal reverse passive Arthus reaction. Mast cell degranulation and the release of TNF during the initiation of inflammation were blocked by decomplementation and C5 deficiency. Mast cell degranulation later in the reaction was complement-independent. Therefore, mast cells were activated in vivo in antibody-mediated injury by two different mechanisms, early in the reaction by complement and later by an unknown stimulus. Both mast cells and intact complement were also required for the full expression of neutrophil influx and release of TNF in the later phase. In fact, activated complement and mast cell mediators seemed to be the only factors necessary for the initiation of neutrophil recruitment. The findings significantly contribute to the understanding of the mechanisms involved in the induction of inflammatory processes in immune complex-mediated injury.
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PMID:Neutrophil elicitation in the reverse passive Arthus reaction. Complement-dependent and -independent mast cell involvement. 830 Nov 39

The family of receptors for IgG (Fc gamma R) plays an essential role in antibody-mediated effector functions of the immune system. However, the specific contribution of each of the Fc gamma R classes to in vivo immune reactions is still unclear. Here, we demonstrate that mice deficient for the ligand-binding alpha chain of Fc gamma RIII lack NK cell-mediated antibody-dependent cytotoxicity and phagocytosis of IgG1-coated particles by macrophages. Strikingly, these mice lack IgG-mediated mast cell degranulation, are resistant to IgG-dependent passive cutaneous anaphylaxis, and exhibit an impaired Arthus reaction. These results indicate a prominent role for Fc gamma RIII in inflammatory and anaphylactic responses, making this receptor a potential target in immunotherapy.
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PMID:Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice. 876 81

Leukocyte adhesion on venules and their emigration to extravascular connective tissue are induced by administration of a nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester. In the present study, the involvement of mast cells in the process was examined in genetically mast cell-deficient and normal rats by intravital microscopy. Superfusion of the NOS inhibitor into the mesentery induced partial degranulation of mast cells in normal rats. However, leukocyte adhesion on mesenteric venules and emigration to extravascular connective tissue occurred even in mast cell-deficient rats, with no significant difference from the normal rats. When the reverse-passive Arthus reaction, characterized by generalized antigen-antibody complex formation, was induced in the rat mesentery, the immune complex increased both the adhesion and emigration in normal rats but not in mast cell-deficient rats. These results show that mast cells are not involved in the leukocyte adhesion and emigration induced by NOS inhibition, but are in the reverse-passive Arthus reaction.
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PMID:Absence of mast cell involvement in leukocyte adhesion and emigration induced by inhibition of nitric oxide synthase. 942 94

We induced the passive reverse Arthus reaction to IgG immune complexes (IC) at different tissue sites in mice lacking C3 treated or not with a C5aR-specific antagonist, or in mice lacking mast cells (Kit(W)/Kit(W-v) mice), and compared the inflammatory responses with those in the corresponding wild-type mice. We confirmed that IC inflammation of skin can be mediated largely by mast cells expressing C5aR and FcgammaRIII. In addition, we provided evidence for C3-independent C5aR triggering, which may explain why the cutaneous Arthus reaction develops normally in C3(-/-) mice. Furthermore, some, but not all, of the acute changes associated with the Arthus response in the lung were significantly more intense in normal mice than in C3(-/-) or Kit(W)/Kit(W-v) mice, indicating for C3- and mast cell-dependent and -independent components. Finally, we demonstrated that C3 contributed to the elicitation of neutrophils to alveoli, which corresponded to an increased synthesis of TNF-alpha, macrophage-inflammatory protein-2, and cytokine-induced neutrophil chemoattractant. While mast cells similarly influenced alveolar polymorphonuclear leukocyte influx, the levels of these cytokines remained largely unaffected in mast cell deficiency. Together, the phenotypes of C3(-/-) mice and Kit(W)/Kit(W-v) mice suggest that complement and mast cells have distinct tissue site-specific requirements acting by apparently distinct mechanisms in the initiation of IC inflammation.
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PMID:Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung. 1144 Nov 11

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury. IC-induced inflammation is mediated by inflammatory cell infiltration, a process highly regulated by expression of multiple adhesion molecules. To assess the role of L-selectin and ICAM-1 in this pathogenetic process, the cutaneous reverse passive Arthus reaction was examined in mice lacking L-selectin (L-selectin(-/-)), ICAM-1 (ICAM-1(-/-)), or both (L-selectin/ICAM-1(-/-)). Edema and hemorrhage, which peaked 4 and 8 h after IC challenge, respectively, were significantly reduced in L-selectin(-/-), ICAM-1(-/-), and L-selectin/ICAM-1(-/-) mice compared with wild-type littermates. In general, edema and hemorrhage were more significantly inhibited in ICAM-1(-/-) mice than in L-selectin(-/-) mice, but were most significantly reduced in L-selectin/ICAM-1(-/-) mice compared with ICAM-1(-/-) or L-selectin(-/-) mice. Decreased edema and hemorrhage correlated with reduced neutrophil and mast cell infiltration in all adhesion molecule-deficient mice, but leukocyte infiltration was most affected in L-selectin/ICAM-1(-/-) mice. Reduced neutrophil and mast cell infiltration was also observed for all mutant mice in the peritoneal Arthus reaction. Furthermore, cutaneous TNF-alpha production was inhibited in each deficient mouse, which paralleled the reductions in cutaneous inflammation. These results indicate that ICAM-1 and L-selectin cooperatively contribute to the cutaneous Arthus reaction by regulating neutrophil and mast cell recruitment and suggest that ICAM-1 and L-selectin are therapeutic targets for human IC-mediated disease.
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PMID:The cutaneous reverse Arthus reaction requires intercellular adhesion molecule 1 and L-selectin expression. 1188 69

Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the relative contribution of adhesion molecules, including selectins and ICAM-1, in this pathogenetic process, the cutaneous passive Arthus reaction was examined in mice lacking E-selectin, P-selectin, or both L-selectin and ICAM-1 with anti-P- or E-selectin mAbs. Edema and hemorrhage were significantly reduced in P-selectin(-/-) mice compared with wild-type mice while they were not inhibited in E-selectin(-/-) mice. Combined E- and P-selectin blockade resulted in more significant reduction relative to L-selectin/ICAM-1(-/-) as well as P-selectin(-/-) mice. Remarkably, both E- and P-selectin blockade in L-selectin/ICAM-1(-/-) mice completely abrogated edema and hemorrhage. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells that expressed significant levels of P-selectin glycoprotein ligand-1. Similarly reduced infiltration of neutrophils and mast cells was observed in the peritoneal Arthus reaction and was associated partly with the decreased production of tumor necrosis factor-alpha and interleukin-6. The results of this study indicate that both endothelial selectins contribute predominantly to the Arthus reaction by regulating mast cell and neutrophil infiltration and that the full development of the Arthus reaction is mediated cooperatively by all selectins and ICAM-1.
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PMID:Relative contributions of selectins and intercellular adhesion molecule-1 to tissue injury induced by immune complex deposition. 1270 29


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