Page 369 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Eosinophils and Eosinophilia

Anna Kovalszki, Peter F. Weller

Eosinophils are terminally differentiated, bone marrow–derived governing this homing of eosinophils to mucosal tissues are
granulocytes that normally circulate in blood in low numbers and not fully known, the chemokine eotaxin-1 is involved in the
tend to localize in those tissues with mucosal epithelial surfaces. homing of eosinophils to the GI tract, but not to the respira-
2
Increased blood or tissue eosinophils occur in helminth parasite tory tract. Eosinophils live longer compared with neutrophils
infections, as well as in allergic diseases and a variety of other, and probably persist in tissues for several weeks. They are
often idiopathic, conditions. Conventionally, the major focus principally tissue-dwelling cells: as demonstrated in rodents, for
on eosinophils has been delineating the “effector” functions every eosinophil present in the circulation, there are 300–500
of these end-stage granulocytes, including what roles these in tissues.
cells play as helminthotoxic effector cells and the contribution
they make to the immunopathogenesis of allergic diseases. Eosinophil Adherence Mechanisms
More recent findings have indicated that eosinophil functions The transit of eosinophils from bone marrow, through the circula-
1-4
are considerably more extensive. Eosinophils contain stores tion, and into tissues is governed, in part, by multiple adherence
of multiple, preformed cytokines; engage in cognate cell–cell molecules expressed on eosinophils (Fig. 24.1). As for other
interactions with other cell types, including lymphocytes; and leukocytes, recruitment of eosinophils into tissue sites of inflam-
have roles in varied host immune and inflammatory responses mation utilizes combinatorial interactions involving specific
not conventionally marked by quantitatively extensive eosinophil adhesion molecules (via their expression and altered affinity
infiltration. 4 states) that mediate cellular interactions with the vascular
endothelium and actions of chemoattractant molecules. Eosino-
phils express several adhesion molecules that they broadly share
PRODUCTION AND DISTRIBUTION with other leukocytes. These adhesion molecules mediate their
OF EOSINOPHILS initial rolling and subsequent adherence to endothelial cells.
Similar to neutrophils, eosinophils can adhere via CD11/CD18
Eosinophilopoiesis heterodimeric β 2 integrins to the intercellular adhesion molecule-1
The development of eosinophils in bone marrow can be elicited and -2 (ICAM-1 and ICAM-2). Likewise, specific sialoglycopro-
by three cytokines. Granulocyte macrophage–colony-stimulating teins mediate adherence between eosinophils and endothelial
factor (GM-CSF), interleukin (IL)-3, and IL-5 all promote E- and P-selectins. Unlike neutrophils, but similar to lymphocytes,
eosinophilopoiesis. In contrast to IL-3 and GM-CSF, which also eosinophils are able to bind to vascular cell adhesion molecule-1
promote the development of other lineages, IL-5 uniquely (VCAM-1). Eosinophils express two α 4 integrins, very late activa-
promotes the development and terminal differentiation of tion antigen-4 (VLA-4, α 4 β 1 ) and α 4 β 7 , which bind to VCAM-1.
5
eosinophils. IL-5 is produced by type 2 innate lymphoid cells, Moreover, α 4 β 7 binds to the mucosal addressin cell adhesion
CD8 T cells, natural killer (NK) cells, and other leukocytes, molecule (MAdCAM). The β 2 integrin αdβ 2 , which binds ICAM-3
including eosinophils themselves. IL-5 is a defining cytokine and is expressed on other leukocytes, is an additional integrin
product of T-helper cell-2 (Th2) CD4 T cells. The production that mediates eosinophil adhesion to VCAM-1. Enhanced expres-
of IL-5 by Th2 lymphocytes accounts for the eosinophilia sion of VCAM-1 on the vascular endothelium, as elicitable by
accompanying T-helper 2 (Th2) cell–mediated immune responses IL-4 or IL-13 stimulation, may contribute to the localization of
characteristic of helminth infections and allergic diseases. eosinophils in some tissue sites of inflammation.
Eosinophilopoiesis develops over about a week. Retained In addition to mediating interactions with the endothelium,
in bone marrow is a pool of mature eosinophils. IL-5, alone eosinophil adherence molecules, by their interactions with
and in concert with the chemokine eotaxin-1 (CCL11), rapidly extracellular matrix components, modulate the activity of
releases this pool of mature eosinophils into the circulation to eosinophils that have exited the bloodstream. Eosinophil VLA-6,
acutely increase blood eosinophilia and facilitate recruitment of α 6 β 1 , binds laminin. Both α 4 β 1 and α 4 β 7 interact with specific
1
eosinophils to sites of inflammation. Blood eosinophils circu- domains of tissue fibronectin, and these interactions can enhance
late with a half-life of about 8–18 hours. Eosinophils leave the eosinophil functional responses. Eosinophils express CD44
circulation and localize in tissues, especially those with mucosal (PGP-1), which binds hyaluronic acid. Siglec-8, a sialic acid–
interfaces with the outside world, such as the gastrointestinal binding immunoglobulin-like lectin, is expressed on eosinophils
(GI) and lower genitourinary tracts. Although the mechanisms and binds sialoglycoconjugates. 6

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