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290 Part IV: Molecular and Cellular Hematology Chapter 19: The Inflammatory Response 291
antigen [HLA]-linked susceptibility in rheumatoid arthritis) are impor- REFERENCES
tant. The characteristics of individual chronic inflammatory responses
are dependent on the location of the injury and the type of injurious 1. Weissman G: Inflammation: Historical perspectives, in Inflammation: Basic Principles
agent. As noted throughout this chapter, the recruitment of mononu- and Clinical Correlates, 2nd ed, edited by JJ Gallin, IM Goldstein, R Snyderman, p 5.
Raven Press, New York, 1992.
clear cells into an inflammatory lesion is governed by the same general 2. Acute and chronic inflammation, in Robbins and Cotran Pathologic Basis of Disease,
paradigm that orchestrates the recruitment of neutrophils into sites of 8th ed, edited by V Kumar, AK Abbas, N Fausto, p 43. Saunders Elsevier, Philadelphia, 2010.
acute inflammation. Unlike most acute conditions, chronic inflamma- 3. Leukocyte migration into tissues, in Cellular and Molecular Immunology, 7th ed, edited
by AK Abbas, AH Lichtman, S Pillai, p 37. Elsevier Saunders, Philadelphia, 2012.
tory processes are sometimes marked by a relatively specific morphol- 4. Angus DC, van der Poll T: Severe sepsis and septic shock. N Engl J Med 369:840, 2013.
ogy (e.g., granuloma formation in tuberculosis, eosinophil infiltration 5. Ortega-Gómez A, Perretti M, Soehnlein O: Resolution of inflammation: An integrated
in parasitic infections) and by the coexistence of tissue repair (i.e., view. EMBO Mol Med 5:661, 2013.
angiogenesis and extracellular matrix production). 6. Innate immunity, in Cellular and Molecular Immunology, 7th ed, edited by AK Abbas,
AH Lichtman, S Pillai, p 55. Elsevier Saunders, Philadelphia, 2012.
A key cell type in chronic inflammatory processes is the macro- 7. Sultani M, Stringen AM, Bowen JM, Gibson RJ: Anti-inflammatory cytokines: Impor-
3,5
phage. Tissue macrophages are derived primarily from circulating tant immunoregulatory factors contributing to chemotherapy-induced gastrointestinal
mucositis. Chemother Res Pract 10:1, 2012.
blood monocytes and can adopt relatively specific functions based 8. Dvorak AM, Feng D: The vesiculo-vacuolar organelle (vvo). A new endothelial cell
on their differentiation in selected body sites (e.g., hepatic Kupffer permeability organelle. J Histochem Cytochem 49:419, 2001.
cells, alveolar macrophages, central nervous system microglia). In 9. Ley KO, Laudanna C, Cybulsky MJ, Nourshargh S: Getting to the site of inflammation:
The leukocyte adhesion cascade updated. Nat Rev Immunol 7:678, 2007.
the setting of chronic inflammation, tissue macrophages can be acti- 10. Chen S, Springer TA: Selectin receptor-ligand bonds: Formation limited by shear rate
vated by immunologic means (IFN-γ secreted by antigen-activated and dissociation governed by the Bell model. Proc Natl Acad Sci U S A 98:950, 2001.
CD4 T lymphocytes) and by nonimmunologic means (microbial 11. Kinashi T: Intracellular signaling controlling integrin activation in lymphocytes. Nat
endotoxin, extracellular matrix proteins and foreign particulates; Rev Immunol 5:546, 2005.
Chap. 67). In turn, activated macrophages enlarge, become more meta- 12. Sim D, Flaumenhoft R, Furie B, Furie B: Interactions of platelets, blood-borne tis-
sue factor, and fibrin during arteriolar thrombus formation in vivo. Microcirculation
bolically active, exhibit enhanced phagocytosis and secrete a large array 12:301, 2005.
3,5
of mediators. Mediators secreted by activated macrophages include 13. Jung U, Key K: Mice lacking two or all three selectins demonstrate overlapping and
distinct functions for each selectin. J Immunol 162:6755, 1999.
proteases, reactive oxygen and nitrogen intermediates, coagulation fac- 14. Jung U, Ramos CL, Bullard DC, Ley K: Gene-targeted mice reveal importance of
tors, arachidonic acid-derived lipids and cytokines. These mediators, as L-selectin-dependent rolling for neutrophil adhesion. Am J Physiol Heart Circ Physiol
detailed in preceding sections, participate in inflammation. Activated 274:H1785, 1998.
macrophages also secrete collagenases that participate in tissue remod- 15. Bajenoff M, Egen JG, Qi H, et al: Highways, byways and breadcrumbs: Directing lym-
phocyte traffic in the lymph node. Trends Immunol 28:346, 2007.
eling, angiogenic factors (e.g., fibroblast growth factor) and profibro- 16. Shimaoka M, Takagi J, Springer TA: Conformational regulation of integrin structure
genic growth factors (fibroblast growth factor, TGF-β, platelet-derived and function. Annu Rev Biophys Biomol Struct 31:485, 2002.
growth factor). Consequently, activated tissue macrophages par- 17. Millard M, Odde S, Neamati N: Integrin targeted therapeutics. Theranostics 1:154, 2011.
3,5
ticipate in inflammation per se, tissue remodeling, angiogenesis and 18. Luscinskas FW, Ma S, Nusrat A, et al: Leukocyte transendothelial migration: A junc-
tional affair. Semin Immunol 14:105, 2002.
fibrosis. 19. Ciacchetti G, Allen PG, Glogauer M: Chemotactic signaling pathways in neutrophils:
Although macrophages play a central role in all facets of chronic From receptor to actin assembly. Crit Rev Oral Biol Med 13:220, 2002.
inflammation, other cell types are also important. Lymphocytes (both 20. Iwakura Y, Ishigame H, Saijo S, Nakae S: Functional specialization of interleukin-17
family members. Immunity 34:149, 2011.
B and T cells) are recruited into chronic inflammatory lesions via 21. Dale DC, Boxer L, Liles WC: The phagocytes: Neutrophils and monocytes. Blood
leukocyte–endothelial adhesive interactions and via chemotactic 112:935, 2008.
mechanisms analogous to those involved in neutrophil recruitment. 22. Nauseef WM: How human neutrophils kill and degrade microbes: An integrated view.
Immunol Rev 219:88, 2007.
Antigen-activated CD4 Th1 lymphocytes produce IFN-γ, which, as dis- 23. Schroder K, Tschopp J: The inflammasomes. Cell 190:821, 2010.
3
cussed above, is an important activator of tissue macrophages. Acti- 24. Takeuchi O, Akira S: Pattern recognition receptors and inflammation. Cell 140:805,
vated CD4 Th2 lymphocytes produce a variety of proinflammatory 2010.
mediators that are involved in lymphocyte activation (e.g., IL-2) and in 25. Blasius AL, Beutler B: Intracellular toll-like receptors. Immunity 32:305, 2010.
26. Kohli P, Levy BD: Resolvins and protectins: Mediating solutions to inflammation. Br J
immune regulation (e.g., IL-5 in IgE production). 3 Pharmacol 158:960, 2009.
Eosinophils and mast cells also play important roles in some types 27. Serhan CN, Chiang N, Van Dyke TE: Resolving inflammation: Dual anti-inflammatory
of chronic inflammation. Mast cells, which tend to be distributed along and pro-resolution lipid mediators. Nat Rev Immunol 8:349, 2008.
48
small blood vessels, possess high-affinity FcεRI receptors for IgE. 28. Stout RD: Macrophage functional phenotypes: No alternatives in dermal wound heal-
ing? J Leukoc Biol 87:19, 2010.
Engagement of mast cell-bound IgE triggers degranulation that leads 29. Martinez FO, Helming L, Gordon S: Alternative activation of macrophages: An immu-
to histamine and arachidonic acid–derived lipid release (Chap. 63). nologic functional perspective. Annu Rev Immunol 27:451, 2009.
Eosinophils are characteristically formed in IgE-mediated allergic reac- 30. Ding T, Deighton C: Complications of anti-TNF therapies. Fut Rheumatol 2:587, 2007.
31. Dean RA, Cox JH, Bellac IL, et al: Macrophage-specific metalloelastase (MMP-12)
tions and in parasitic infections (Chap. 62). Eotaxin, a CC chemokine, truncates and inactivates ELR + CXC chemokines and generates CCL2, -7, -8, and -13
binds to and activates eosinophils via CCR3. Recruited eosinophils antagonists: Potential role of the macrophage in terminating polymorphonuclear leu-
3,48
kocyte influx. Blood 112: 3455, 2008.
secrete various granule proteins that help kill parasites, but which can 32. Babior BM: Phagocytes and oxidative stress. Am J Med 109:33, 2003.
also cause tissue damage. As inferred above, the histopathologic appear- 33. Bosmann M, Ward PA: Invited review. The inflammatory response in sepsis. Trends
ance of many chronic inflammatory lesions can provide insight into Immunol 34:129, 2013.
their pathogenesis and cause. A variety of poorly degraded, intrinsi- 34. Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of
arterial smooth muscle by acetylcholine. Nature 288:373, 1980.
cally low toxicity agents can induce granulomatous inflammation (e.g., 35. Laroux FS, Pavlick KP, Hines IN, et al: Role of nitric oxide in inflammation. Acta Physiol
49
M. tuberculosis). Many parasites induce an eosinophilic response (e.g., Scand 173:113, 2001.
Toxocara canis). Finally, the induction of tissue remodeling, angiogen- 36. Sims JE, Smith DE: The IL-1 family: Regulators of immunity. Nat Rev Immunol 10:89,
2010.
esis and fibrosis can contribute to both tissue damage and repair, and 37. Bromley SK, Mempel TR, Lyster AD: Orchestrating the orchestrators: Chemokines in
can also suggest underlying etiology (e.g., lung fibrosis associated with control of T cell traffic. Nat Immunol 9:970, 2008.
asbestos). The tremendous advances in understanding of the inflamma- 38. Sallusto F, Baggiolini M: Chemokines and leukocytes traffic. Nat Immunol 9:949, 2008.
tory response hold great promise for the future of both diagnostics and 39. Lu B, Rutledge BJ, Gu L, et al: Abnormalities in monocyte recruitment and cytokine
therapeutics. expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med 187:601,
1998.
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