Mast cells are hematopoietic cells that reside in virtually all vascularized tissues and that represent potential sources of a wide variety of biologically active secreted products, including diverse cytokines and growth factors. There is strong evidence for important non-redundant roles of mast cells in many types of innate or adaptive immune responses, including making important contributions to immediate and chronic IgE-associated allergic disorders and enhancing host resistance to certain venoms and parasites. However, mast cells have been proposed to influence many other biological processes, including responses to bacteria and virus, angiogenesis, wound healing, fibrosis, autoimmune and metabolic disorders, and cancer. The potential functions of mast cells in many of these settings is thought to reflect their ability to secrete, upon appropriate activation by a range of immune or non-immune stimuli, a broad spectrum of cytokines (including many chemokines) and growth factors, with potential autocrine, paracrine, local, and systemic effects. In this review, we summarize the evidence indicating which cytokines and growth factors can be produced by various populations of rodent and human mast cells in response to particular immune or non-immune stimuli, and comment on the proven or potential roles of such mast cell products in health and disease.

Anaphylaxis is an acute, severe, and potentially fatal systemic allergic reaction. Immunoglobulin E (IgE), mast cells, and histamine have long been associated with anaphylaxis, but an alternative pathway mediated by IgG has been suggested to be more important in the elicitation of anaphylaxis. Here, we showed that basophils, the least common blood cells, were dispensable for IgE-mediated anaphylaxis but played a critical role in IgG-mediated, passive and active systemic anaphylaxis in mice. In vivo depletion of basophils but not macrophages, neutrophils, or NK cells ameliorated IgG-mediated passive anaphylaxis and rescued mice from death in active anaphylaxis. Upon capture of IgG-allergen complexes, basophils released platelet-activating factor (PAF), leading to increased vascular permeability. These results highlight a pivotal role for basophils in vivo and contrast two major, distinct pathways leading to allergen-induced systemic anaphylaxis: one mediated by basophils, IgG, and PAF and the other "classical" pathway mediated by mast cells, IgE, and histamine.

Ticks are ectoparasitic arthropods that can transmit a variety of microorganisms to humans and animals during blood feeding, causing serious infectious disorders, including Lyme disease. Acaricides are pharmacologic agents that kill ticks. The emergence of acaricide-resistant ticks calls for alternative control strategies for ticks and tick-borne diseases. Many animals develop resistance to ticks after repeated infestations, but the nature of this acquired anti-tick immunity remains poorly understood. Here we investigated the cellular and molecular mechanisms underlying acquired resistance to Haemaphysalis longicornis ticks in mice and found that antibodies were required, as was IgFc receptor expression on basophils but not on mast cells. The infiltration of basophils at tick-feeding sites occurred during the second, but not the first, tick infestation. To assess the requirement for basophil infiltration to acquired tick resistance, mice expressing the human diphtheria toxin receptor under the control of the mast cell protease 8 (Mcpt8) promoter were generated. Diphtheria toxin administration to these mice selectively ablated basophils. Diphtheria toxin-mediated basophil depletion before the second tick infestation resulted in loss of acquired tick resistance. These data provide the first clear evidence, to our knowledge, that basophils play an essential and nonredundant role in antibody-mediated acquired immunity against ticks, which may suggest new strategies for controlling tick-borne diseases.

IntroductionBasophils are the least common leukocytes in the peripheral blood and account for only approximately 0.5% of all leukocytes. Like mast cells, basophils express the high-affinity IgE receptor Fc⑀RI on their cell surface, and they release chemical mediators such as histamine and leukotriene C4 upon stimulation. [1][2][3][4][5] Therefore, basophils have often been neglected or considered minor and possibly redundant "circulating mast cells" and analyzed as a surrogate of the less accessible tissue mast cells. 6 However, basophils and mast cells differ in their natural history. Even though both originate from hematopoietic stem cells in the bone marrow, basophils complete their differentiation in the bone marrow, whereas mast cells do so in the peripheral tissues. 5,7 Basophils circulate in the peripheral blood and do not migrate into the peripheral tissues under physiologic conditions, while mature mast cells reside in the peripheral tissues and do not circulate in the peripheral blood. The lifespan of basophils is several days, much shorter than that of mast cells, and basophils do not proliferate once they mature, unlike mast cells. These differences strongly suggest that basophils and mast cells play distinct roles in vivo.Mast cells and basophils have long been considered primary effector cells in allergic disorders such as anaphylaxis, hay fever, and asthma. 5,7 Recent works demonstrated that mast cells actively participate in the innate immune responses to many pathogens, including bacteria and virus. 8 In addition to such roles as effector cells, recent evidence indicates that mast cells can also play immunoregulatory roles. 9 Mast cells influence the sensitization phase of some acquired immune responses, 10 and contribute to the pathology of autoimmune disorders [11][12][13] and to the expression of peripheral tolerance. 14 Compared with extensive investigation on mast cells and advances in our understanding of mast cell functions, the in vivo roles of basophils are far less studied and defined.A clue to clarifying critical and nonredundant roles of basophils has been provided by the recent finding that basophils readily generate large quantities of T helper 2 (Th2) cytokines such as IL-4 and IL-13 in both humans and mice. [15][16][17][18] These cytokines are the key regulators in conditioning the immune response to the Th2 type. Basophil-derived IL-4 has been shown to drive the differentiation of naive CD4 T cells to Th2 cells in vitro and in vivo. 19,20 Basophils also stimulate B cells to synthesize IgE in vitro in an IL-4-and CD40L-dependent manner. 21,22 We recently identified a novel type of chronic allergic inflammation designated IgEmediated chronic allergic inflammation (IgE-CAI) that requires the presence of basophils, but not mast cells or T cells. 23 A single subcutaneous injection of multivalent antigens elicited not only immediate-and late-phase ear swelling but also delayed-onset ear swelling with massive eosinophil infiltration in mice sensitized with antigen-specific IgE or in mi...