Eosinophils

Although eosinophils are usually considered as major contributors to host defenses against helminths, they resemble neutrophils in possessing chemotactic, phagocytic and microbicidal activity. Eosinophils kill bacteria and fungi by oxidative and nonoxidative mechanisms, although the composition of their molecular armamentarium differs from that of neutrophils. For example, instead of myeloperoxidase, which catalyzes the generation of hypochlorous acid and chloramines in neutrophils, eosinophils contain a structurally distinct peroxidase that produces hypobromous acid and bromamines. The principal nonoxidative microbicidal polypeptides of eosinophils include major basic protein (MBP) and eosinophil cationic protein (ECP), both of which also kill helminths and protozoa. MBP is a small, basic and arginine-rich peptide (pi 10.9, M,. 13.S'kDa) that comprises up to 50% of the total protein in guinea pig eosinophil granules. ECP is a larger molecule (M,. 18-21 kDa) that contains a high content of arginine, proline and cystine (pi >11). Unlike MBP, which occupies the crystalloid core of the eosinophil's distinctive cytoplasmic granule, ECP is located in the granule's matrix. ECP shows sequence homology to ribonucleases and demonstrates ribonuclease acivity. ECP and MBP killed E. coli by similar but nonident-ical mechanisms, each marked by a sequential attack on the organism's outer and inner membranes. ECP

also forms relatively nonselective pores in artificial model membranes.

Mononuclear phagocytes

Although monocytes and macrophages play crucial roles in host defense against facultative and obligate intracellular parasites, their nonoxidative mechanisms for killing intracellular organisms or inhibiting their replication are not well understood. This may be due to the inherent complexity of the mononuclear phagocyte system, interspecies differences and the multiple effects of activation, differentiation and immunoregulatory cytokines on macrophage composition and function. It may also be that macrophages follow 'just-in-time' manufacturing principles for producing antimicrobial peptides and proteins, rather than stockpiling them in cytoplasmic granules in the manner of neutrophils and eosinophils. Strong evidence supporting the existence of nonoxidative antimicrobial mechanisms has been adduced from studies with diverse organisms, including Toxoplasma gondii, Trypanosoma cruzi, Chlamydia psittaci, Candida albicans, Aspergillus fumi-gatus, Mycobacterium bovis and Mycobacterium tuberculosis. Most macrophages contain lysozyme and type 2 phospholipase A,, and some, such as rabbit alveolar macrophages, contain defensins. There is evidence for histone-like antimicrobial proteins in various macrophages, although their significance for antimicrobial function remains to be established. Under some circumstances, macrophage enzymes such as arginase and indoleamine 2,3-dioxygenase may exert antimicrobial effects by depleting the environment of arginine and tryptophan, respectively. The possibility that macrophages recvcle and use antimicrobial molecules initially synthesized by other cells, such as neutrophils, warrants consideration and is supported by some experimental evidence and the presence of receptors for neutrophil-derived molecules, such as lactoferrin and BP1, and the ability of macrophages to acquire neutrophil-derived molecules by pinocytosis.

See also: Degranulation; Eosinophils; Microbicidal mechanisms, oxygen-dependent; Monocytes; Mononuclear phagocyte system; Neutrophils; Phagocytosis.

Further reading

Elsbach P and Weiss J (1992) Oxygen-independent antimicrobial systems of phagocytes. In: Gallin JI, Goldstein IM and Synderman R (eds) Inflammation. Basic Principles and Clinical Correlates, 2nd edn, pp 603-637. New York: Raven Press. Gabay JE and Almeida RP (1993) Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin. Current Opinion in Immunology 5: 97-102. Ganz T and Lehrer RI (1994) Defensins. Current Opinion in Immunology 6: 584-589. Marsh J and Good JA (eds) (1994) Antimicrobial peptides.

Ciba Foundation Symposium 186: 1-283. Metchnikoff E (1905) immunity in Infective Diseases, translated by FG Binnie. Cambridge: Cambridge University Press.

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