Cell derived mediators

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

In this article we will describe the possible roles of cardiac mast cells and their mediators during anaphylactic reactions in man and will briefly review the cardiovascular effects of mast cell-derived mediators in vivo. 

Fig.1. Mast cells bridge innate and adaptive immunity. Activation of mast cells by TLR ligands induces a fast local inflammatory response. Mast cell-derived mediators also promote the migration of antigen-laden LCsfrom the skin to the regional LNs, where a specific adaptive immune response is induced.

Polosa R, Ng WH, Crimi N, Vancheri C, Holgate ST, Church MK, Mistretta A (1995) Release of mast-cell-derived mediators after endobronchial adenosine challenge in asthma. Am 1 Respir Crit Care Med 151(3 Pt l) 624-629... 

In addition to cell-derived mediators, several acellular biochemical cascade systems act in parallel to initiate and propagate the inflammatory response. These include ... 

Cell-derived Mediators Implicated in 6.6.5 Neutrophil-derived Toxic ... 

Many cell-derived mediators are likely to have roles in these processes of cellular injury. However, our knowledge of the precise functions of many of these candidates is currendy limited. This is most outstandingly true for the MMPs and their inhibitors, where despite a vast literature on their function in other tissues, there is only a poor understanding of their possible function in the lung. Clearly, further understanding of the mechanisms of pulmonary repair and fibrosis will be necessary to gain a full appreciation of their possible roles and relevance in injury and repair. 

Delineation of the role of a specific mediator in the bronchomotor response to a proinflammatory stimulus is usually obtained by the ability of a specific receptor antagonist to block the response. This process of identification is dependent on the antagonist s being applied in doses sufficient to block the receptor for the endogenously released mediator and selective for the receptor of the mediator at the applied doses. Specific antagonists have been developed or are currently being developed for many of the inflammatory cell-derived mediators possessing bronchoconstrictor or proinflammatory activity. 

HCV has been associated with many extrahepatic manifestations [35, 36, 67], including myocarditis and cardiomyopathy [68, 69]. Histological and functional observations have led to the hypothesis that mast cells play an important role in many fibrotic reactions [70-72], Potential mast cell-derived mediators of the fibrotic response include histamine, tryptase and TGF-fl, which stimulate fibroblast proliferation and collagen synthesis [73-75]. By producing these factors, chronic activation of cardiac mast cells by protein Fv may contribute to the heart fibrosis found in some patients with HCV infection [68, 69]. 

Church MK, Shute JK, Jensen HM. Mast cell-derived mediators. In Adkinson NF, Yunginer JW, Busse WW, et al., eds. Middleton s Allergy Principles and Practice. 6th Ed. Philadelphia Mosby 2003 189-212. 

Austen KF, Wasserman SI, Goetzel EJ. Mast cell-derived mediators structural and functional diversity and regulation of expression. In S. Johanson SGO, Strandeng K, Uvnas B, eds. Molecular Aspects of the Acute Allergic Reactions. New York Plenum Press, 1976 293. 

Siraganian RP. Biochemical events in basophil or mast cell activation and mediator release. In Middleton E, Reed CE, Ellis EF, Adkinson F, Yuninger JW, Busse WW, eds. Allergy Principles and Practice. Vol. 1. St. Louis Mosby, 1998 204-227. Church MK, Holgate ST, Shute JK, Walls AF, Sampson AP. Mast Cell-Derived mediators. In Middleton E, Reed CE, Ellis EF, Adkinson NF, Yuninger JW, Busse WW, eds. Allergy Principles and Practices. Vol. 1. St. Louis Mosby-Year Book, Inc., 1998 146-167. 

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