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Chapter 6 : Roles of Mast Cells and Basophils in Innate Immunity

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Abstract:

This chapter reviews basic aspects of mast cell and basophil development and function, describes a mouse model for analyzing mast cell function in vivo, and then outlines the evidence that mast cells and/or basophils can contribute to innate immune responses. Both mast cells and basophils are derived from CD34 hematopoietic progenitor cells present in adult blood and bone marrow, and these two cell types share many similarities in mediator content, surface receptor expression, and function. Mice that genetically lack only mast cells or basophils would represent ideal model animals for investigating the contributions of these two cell types to specific pathological or physiological processes. The mast cell knock-in mouse model has been used by several groups to show that mast cells can represent an important component of host defense against bacterial infection. Studies of mast cells and basophils in host defense against parasites have focused predominantly on the potential roles of these cells in acquired, rather than innate, immune responses. The studies in the cecal ligation and puncture (CLP) model in mice, and other lines of evidence, support the view that mast cells can have sentinel and effector functions in innate immunity to bacteria. The mast cell, so rightly considered a key “part of the problem” in the expression of anaphylaxis, atopic asthma, and other immunoglobulin E (IgE)-associated disorders, clearly can provide significant benefit in host defense during certain examples of bacterial infection, at least in mice.

Citation: Galli S, Chatterjea D, Tsai M. 2004. Roles of Mast Cells and Basophils in Innate Immunity, p 111-132. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch6

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FIGURE 1

Long-term subcutaneous treatment of C57BL/6 mice (male, 6 to 9 weeks old) with SCF results in increased numbers of dermal and peritoneal mast cells and enhanced survival after CLP. (A and B) Some mice were killed after the last of 21 daily subcutaneous injections with vehicle, rat recombinant SCF ( ) (rrSCF, 50, 100, or 200 μg/kg per day), or polyethylene glycol-derivatized rrSCF ( ) (rrSCF-peg, 30 or 100 μg/kg per day), for assessment of (A) the numbers of mast cells per mm of dermis at the site of injections and (B) the numbers of mast cells in peritoneal lavage fluid; data in panel A also include values for some mice in panel C that died within 2 days of CLP. Numbers of mice per group are indicated inside the bars; in A, fold change (i.e., value for SCF-treated group and value for vehicle-treated group) is given in parentheses. *** < 0.005 versus values for mice treated with vehicle alone. (C) Some mice (male, 6 to 9 weeks old) were treated daily for 21 days before CLP and for 14 days or until death after CLP (~50% ligation, single puncture with a 0.7-mm needle); mice received subcutaneous injections of vehicle, 50-, 100-, or 200-μg/kg per day rrSCF, or 30- or 100-μg/kg per day rrSCF-peg ( = 138, 18, 58, 30, 30, and 30, respectively). Data were pooled from at least three independent experiments per treatment group. PLF, peritoneal lavage fluid. Reproduced from Fig. 1 of with permission of the publisher.

Citation: Galli S, Chatterjea D, Tsai M. 2004. Roles of Mast Cells and Basophils in Innate Immunity, p 111-132. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch6
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Image of FIGURE 2
FIGURE 2

Long-term subcutaneous treatment with SCF increases (A) the numbers of mast cells in the peritoneal lavage fluid (PLF) and (B) survival (%) at day 14 after CLP in WT mice and in mast cell-reconstituted / mice, but not in mast cell-deficient / mice. (A) Number of mast cells in the PLF: three to five mice per group (male, 11 to 13 weeks old at time of death or CLP) were killed after the last of 21 daily subcutaneous injections with vehicle or rrSCF-peg (30 μg/kg per day) for assessment of the numbers of mast cells in PLF. (B) Survival (%) of mice at 14 days after CLP: 24 to 27 mice per group were treated daily for 21 days before CLP and for 14 days or until death after CLP (∼50% ligation, single puncture with a 0.7-mm needle). values in parentheses are for survival after day 3. Data were pooled from two independent experiments per treatment group. Significance of differences in overall (0 to 14 days) or late-phase (>3 days after CLP) survival in the mice was calculated by the Mantel-Cox log rank test. Modified, with permission, from Fig. 2 of with permission of the publisher.

Citation: Galli S, Chatterjea D, Tsai M. 2004. Roles of Mast Cells and Basophils in Innate Immunity, p 111-132. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch6
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Tables

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TABLE 1

Natural history, major mediators, and surface membrane structures of human mast cells and basophils

Citation: Galli S, Chatterjea D, Tsai M. 2004. Roles of Mast Cells and Basophils in Innate Immunity, p 111-132. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch6
Generic image for table
TABLE 2

Features of CLP in WT (+/+), C3, or human C3 (HuC3)-treated C3 mice

Citation: Galli S, Chatterjea D, Tsai M. 2004. Roles of Mast Cells and Basophils in Innate Immunity, p 111-132. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch6

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