Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines.

Abstract

Mast cells (MC)l are widely distributed throughout vascularized tissues and certain epithelia. They represent a source ofpotent mediators ofinflammation (reviewed in references 1-4). These mediators are released after sensitization with IgE immunoglobulins, which are bound to IgE receptors (FceRI) on the MC, and crosslinking with specific multivalent antigen (4). Such activation causes MC to degranulate releasing histamine, heparin, and other sulphated proteoglycans and certain neutral proteases. Activated MC also elaborate newly synthesized mediators such as products of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism (reviewed in references 2-4). MC are widely regarded as critical effector cells in the inflammatory reactions underlying disorders of IgE-dependent immediate hypersensitivity and in the expression ofprotective immunity involving IgE (reviewed in references 1-4).Studies in mice indicate that MC are derived from multipotential bone marrowderived hematopoietic precursors which complete their program of differentiation and maturation in vascularized tissues, epithelia, and serosal cavities (reviewed in references 1, 5). This process results in the generation ofmast cell populations which vary in multiple aspects of their phenotype, including morphology, mediator content, and sensitivity to regulation by cytokines affecting proliferation and maturation (reviewed in reference 1). One such population, referred to as "mucosal" mast cells (MMC) because they occur in the mucosal layer of gastrointestinal tissues, appears to be exquisitely sensitive to regulation by the T cell-associated cytokines IL-3 and IL-4 (1). IL-3 probably represents the major cytokine regulating proliferation ofthis subset (6, 7), whereas in vitro studies indicate that IL-4 can act as a costimulant of proliferation (8). Thus, the mouse MMC population is regulated by products I Abbreviations used in this paper: AbMuLV, Abelson murine leukemia virus; Ag, antigen; BMCMC, bone marrow-derived cultured mast cell ; DNP3o-40-HSA 2,4-dinitrophenyl-human serum albumin; FceRI, cell surface receptor for the Fc portion of IgE; GM-CSF, granulocyte/macrophage colony-stimulating factor ; MC, mast cell; MIP, macrophage inflammatory protein; MMC, mucosal mast cell ; PKC, protein kinase C. J. Exp. MED.

Contribution of Fibroblast and Mast Cell (Afferent) and Tumor (Efferent) IL-6 Effects within the Tumor Microenvironment

“…On the other hand, it is becoming increasingly evident that mast cells contribute to tumor growth through their positive effects on tumor blood vessel development, extracellular matrix remodelling (as a subversion to ECM remodelling in wound healing) and ability to modulate immune responses (reviewed in [35]). In addition, activated mast cells release IL-6 (reviewed in [31,36,37]), which could contribute to breast tumor invasiveness [25].…”

“…Since active, degranulating mast cells secrete IL-6 (reviewed in [31,36,37]) and IL-6 is important for mast cell development [40], and given the potential role of mast cells in the tumor stroma, we went back to our xenograft models to examine whether mast cells were present.…”

Role of infiltrated leucocytes in tumour growth and spread

“…However, several types of tumours produce stem cell factor that may have functions in mast cell migration, proliferation and activation (Turner et al, 1992). In addition to the promotion of angiogenesis, the activated mast cells are a rich source of cytokines and chemokines such as IL-1, IL-3, IL-4, IL-8, granulocyte -macrophage colony-stimulating factor, TNFa, interferon-g (IFNg), CCL-2, Macrophage Inflammatory Protein MIP-1a and b, many of which can contribute to the tumour microenvironment by enhancing tumour cell growth and invasion either directly or through intermediaries such as macrophages (Burd et al, 1989;Selvan et al, 1994).…”

Augmentation of reverse arthus reaction by mast cells in mice.

“…Antihistamines will decrease plasma leakage during immune complex reactions (34). It has recently been reported that mast cells upon stimulation with a number of agents, including IgE/Ag, calcium ionophore, and PMA, will cause the induction of various cytokines, such as IL-1, IL-3, IL-4, IL-6, GM-CSF, and TNFa (35)(36)(37) (42).…”