Chitins and chitosans as immunoadjuvants and non-allergenic drug carriers.
Due to the fact that some individuals are allergic to crustaceans, the presumed relationship between allergy and the presence of chitin in crustaceans has been investigated. In vivo, chitin is part of complex structures with other organic and inorganic compounds: in arthropods chitin is covalently linked to proteins and tanned by quinones, in fungi it is covalently linked to glucans, while in bacteria chitin is diversely combined according to Gram(+/-) classification. On the other hand, isolated, purified chitin is a plain polysaccharide that, at the nano level, presents itself as a highly associated structure, recently refined in terms of regularity, nature of bonds, crystallinity degree and unusual colloidal behavior. Chitins and modified chitins exert a number of beneficial actions, i.e., (i) they stimulate macrophages by interacting with receptors on the macrophage surface that mediate the internalization of chitin particles to be degraded by lysozyme and N-acetyl-beta-glucosaminidase (such as Nod-like, Toll-like, lectin, Dectin-1, leukotriene 134 and mannose receptors); (ii) the macrophages produce cytokines and other compounds that confer non-specific host resistance against bacterial and viral infections, and anti-tumor activity; (iii) chitin is a strong Th1 adjuvant that up-regulates Th1 immunity induced by heat-killed Mycobacterium bovis, while down- regulating Th2 immunity induced by mycobacterial protein; (iv) direct intranasal application of chitin microparticles into the lung was also able to significantly down-regulate allergic response to Dermatophagoids pteronyssinus and Aspergillus fumigatus in a murine model of allergy; (v) chitin microparticles had a beneficial effect in preventing and treating histopathologic changes in the airways of asthmatic mice; (vi) authors support the fact that chitin depresses the development of adaptive type 2 allergic responses. Since the expression of chitinases, chitrotriosidase and chitinase-like proteins is greatly amplified during many infections and diseases, the common feature of chitinase-like proteins and chitinase activity in all organisms appears to be the biochemical defense of the host. Unfortunately, conceptual and methodological errors are present in certain recent articles dealing with chitin and allergy, i.e., (1) omitted consideration of mammalian chitinase and/or chitotriosidase secretion, accompanied by inactive chitinase-like proteins, as an ancestral defensive means against invasion, capable to prevent the insurgence of allergy; (2) omitted consideration of the fact that the mammalian organism recognizes more promptly the secreted water soluble chitinase produced by a pathogen, rather than the insoluble and well protected chitin within the pathogen itself; (3) superficial and incomplete reports and investigations on chitin as an allergen, without mentioning the potent allergen from crustacean flesh, tropomyosine; (4) limited perception of the importance of the chemical/biochemical characteristics of the isolated chitin or chitosan for the replication of experiments and optimization of results; and (5) lack of interdisciplinarity. There is quite a large body of knowledge today on the use of chitosans as biomaterials, and more specifically as drug carriers for a variety of applications: the delivery routes being the same as those adopted for the immunological studies. Said articles, that devote attention to the safety and biocompatibility aspects, never reported intolerance or allergy in individuals and animals, even when the quantities of chitosan used in single experiments were quite large. Therefore, it is concluded that crab, shrimp, prawn and lobster chitins, as well as chitosans of all grades, once purified, should not be considered as "crustacean derivatives", because the isolation procedures have removed proteins, fats and other contaminants to such an extent as to allow them to be classified as chemicals regardless of their origin.
Muzzarelli
Riccardo A A
RA
University of Ancona, Ancona, Italy. Muzzarelli.raa@gmail.it
D054392:Adipokines; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology; D002686:Chitin / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000378:metabolism; D048271:Chitosan / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology; D037102:Lectins / Q000502:physiology
D054392:Adipokines; D000276:Adjuvants, Immunologic; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D004337:Drug Carriers; D006023:Glycoproteins; D037102:Lectins; D002686:Chitin; D048271:Chitosan; D002688:Chitinases
Clin Chim Acta. 1991 Jun 14;199(2):185-94
1908363
Respir Med. 2007 Oct;101(10):2176-81
17631992
J Immunol. 1996 Nov 1;157(9):4173-80
8892655
Keio J Med. 2007 Mar;56(1):21-7
17392594
Chest. 2007 Sep;132(3):1007-14
17873195
Cell Mol Immunol. 2009 Feb;6(1):45-50
19254479
Infect Immun. 1997 May;65(5):1734-41
9125555
Clin Exp Allergy. 2006 Jul;36(7):960-8
16839412
Yonsei Med J. 2009 Feb 28;50(1):22-30
19259344
Science. 2004 Jun 11;304(5677):1577
15192186
J Allergy Clin Immunol. 2004 Aug;114(2):459-60
15341031
EXS. 1999;87:279-92
10906967
J Clin Lab Anal. 2005;19(3):128-32
15900564
Protein Sci. 2009 Mar;18(3):569-78
19241384
J Exp Med. 2008 Jan 21;205(1):13-7
18195077
Eur J Pharm Sci. 2008 Feb 5;33(2):166-76
18248966
J Exp Med. 1995 Nov 1;182(5):1527-36
7595222
J Immunol. 2003 Oct 1;171(7):3655-67
14500663
J Allergy Clin Immunol. 2005 Sep;116(3):497-500
16159614
J Allergy Clin Immunol. 2008 Jul;122(1):202-8, 208.e1-7
18602573
EXS. 1999;87:211-21
10906962
Clin Chem Lab Med. 2005;43(5):499-502
15899671
J Proteome Res. 2009 Apr;8(4):1631-8
19714806
EMBO J. 2005 Mar 23;24(6):1277-86
15729357
Curr Opin Immunol. 2008 Dec;20(6):684-9
18938241
J Pharm Pharmacol. 2009 Jan;61(1):3-12
19126291
Crit Rev Clin Lab Sci. 2008;45(6):531-62
19003601
Biochem J. 2009 Apr 28;420(1):1-16
19382893
Clin Lab. 2007;53(5-6):321-33
17605408
N Engl J Med. 2007 Nov 15;357(20):2016-27
18003958
J Biol Chem. 2000 Oct 20;275(42):32721-7
10827089
J Clin Invest. 2006 Jun;116(6):1642-50
16710478
Am J Respir Crit Care Med. 2009 Mar 15;179(6):449-56
19106306
J Allergy Clin Immunol. 2003 Mar;111(3):450-63; quiz 464
12642820
Microbiol Immunol. 1984;28(8):903-12
6094990
Expert Opin Drug Deliv. 2009 Mar;6(3):239-53
19290841
Infect Immun. 2005 Jan;73(1):385-94
15618176
Nat Rev Immunol. 2003 Jan;3(1):23-35
12511873
Biomaterials. 2008 May;29(14):2173-82
18279951
J Biol Chem. 2001 May 18;276(20):17497-506
11297523
Int J Pharm. 2009 Jul 30;377(1-2):120-7
19454304
Nature. 2007 May 3;447(7140):92-6
17450126
Science. 2004 Jun 11;304(5677):1678-82
15192232
Clin Exp Allergy. 2002 Dec;32(12):1794-800
12653174
Clin Exp Dermatol. 2009 Jan;34(1):55-60
19076793
N Engl J Med. 2007 Nov 15;357(20):2082-4
18003965
Annu Rev Immunol. 2007;25:193-219
17129180
Trends Parasitol. 2004 Mar;20(3):126-33
15036034
Cell. 2006 Feb 24;124(4):783-801
16497588
J Immunol. 2007 Oct 15;179(8):5367-77
17911623
Int Arch Allergy Immunol. 2009;149(4):369-77
19295241
Curr Opin Allergy Clin Immunol. 2009 Feb;9(1):60-6
19532094
J Allergy Clin Immunol. 2008 Nov;122(5):944-950.e3
18845328
J Immunol. 2009 Mar 15;182(6):3573-82
19265136
N Engl J Med. 2008 Mar 6;358(10):1073-5; author reply 1075
18322291
Acta Biomater. 2007 Nov;3(6):882-95
17572163
Acta Biomater. 2007 May;3(3):301-9
17208527
J Pharm Sci. 2009 May;98(5):1643-56
18781621
Immunobiology. 2009;214(2):87-99
19167987
Trends Immunol. 2007 Oct;28(10):419-22
17826333
J Immunol. 2000 Feb 1;164(3):1314-21
10640745
Gastroenterology. 2006 Feb;130(2):398-411
16472595
Clin Chim Acta. 2003 May;331(1-2):79-85
12691867
Viral Immunol. 2003;16(4):541-7
14733740
Lab Invest. 2008 Aug;88(8):883-95
18490894
Clin Exp Allergy. 2006 Nov;36(11):1457-61
17083356
Mar Biotechnol (NY). 2003 Jul-Aug;5(4):339-48
14719162
Vaccine. 1984 Mar;2(1):93-9
6397928
J Immunol. 1997 Sep 1;159(5):2462-7
9278339
Am J Respir Cell Mol Biol. 2008 Nov;39(5):530-5
18474671
Clin Exp Allergy. 2009 Jul;39(7):943-55
19400900
Infect Immun. 2001 Oct;69(10):6123-30
11553551
Curr Opin Biotechnol. 1998 Jun;9(3):270-7
9650272
BMC Immunol. 2002 Jul 04;3:7
12098359
J Immunol. 2005 May 15;174(10):6346-56
15879135
Carbohydr Res. 1986 Feb 1;146(2):251-8
3955576
J Infect Chemother. 2008 Apr;14(2):86-92
18622669