The 434(G>C) polymorphism within the coding sequence of Eosinophil Cationic Protein (ECP) correlates with the natural course of Schistosoma mansoni infection

Structural determinants of the eosinophil cationic protein antimicrobial activity

“…Recent genomic studies revealed a polymorphism at the coding sequence (Arg97Thr), which correlates with asthma predisposition and parasitic infection susceptibility (Eriksson et al , 2007a ). Indeed, eosinophilia and specifi c eosinophil tissue infi ltration are directly associated with parasite infections (Klion and Nutman , 2004 ;Bystrom et al , 2011 ;Makepeace et al , 2012 ).…”

“…A similar scenario was reported for Schistosoma infection, a common helminth parasite in tropical areas. Eosinophils participate not only in the host protection against schistosomes but also contribute to the derived pathogenesis, as fi brosis development and also the non-toxic variant would have been selected (Eriksson et al , 2007a ).…”

“…In fact, the proteolytic processing is used extensively in immunology cascade events. A local cleavage can release the active peptides in the infection area in the same manner as cecropin is released from cathelicidins expressed in neutrophils (Zanetti et al , 1995 ;Burton and Steel , 2009 ), lactoferricin is derived from the N-terminus (Krieg et al , 1998 ;Clark et al , 2003 ); Tyr33 nitration (Ulrich et al , 2008 ) Host defense against viral infections; chemotaxis for dendritic cells (Rosenberg , 2008a ) RNase 3 (tested against several Gram-negative and -positive species (Torrent et al , 2009b(Torrent et al , , 2011b Arg97/Thr (related to asthma propensity and disease-induced pathologies) (Eriksson et al, 2007a;Adu et al , 2011 ) Gly103Arg 3 potential N-glycosylation sites; 10 purifi ed variants of N-linked glycosylated forms (Eriksson et al , 2007b ); N-glycosylation processed upon secretion by activated eosinophils (Woschnagg et al , 2009 );…”

Eosinophil catonic protein – current concepts and controversies

“…Due to G>C sub sti tu tion, the co don for the ami no acid ar gi ni ne is chan ged in the co don for threo ni ne, whi ch lea ds to the chan ge in Ar g97Thr in the ECP pro tein. The consequen ce of the chan ge in ami no acid struc tu re is al te ra tion of bio lo gi cal ac ti vi ty of the ECP mo le cule be cau se Ar g97 is im por ta nt for the cyto toxic acti vi ty of ECP (19,20). The sub sti tu tion of ar gi ni ne at po si tion 97 wi th threo ni ne al lows the for ma tion of a new, four th glyco syla tion si te at po si tion 95 (EC-P 95Asn ), and en han ced glyco syla tion of ECP pro tein dec rea ses its cyto toxic ac ti vi ty.…”

“…Pa ra si ta ry in fec tio ns, as thma and ma ligna nt di sea ses are on ly so me pat ho lo gi cal con di tions wi th ECP in vol ve me nt in their pat ho mec ha nisms so that di sea se out co me is as so cia ted wi th ECP phe no type or ge no type. Thus, in di vi dua ls in fec ted wi th Schis to so ma man so ni (S. man so ni) pa ra si te, who are at the sa me ti me car rie rs of the ECP 434GG cyto toxic ge no type, ha ve bet ter pri ma ry de fen se reac tion com pa red wi th in fec ted in di vi dua ls wi th ot her ge no types, but al so de ve lop con si de rab ly mo re frequen tly a se rious and li fe-threa te ni ng com pli ca tio ns li ke he pa tic fi b ro sis (19). The pre valen ce of in di vi dual ECP 434 ge no type in pa tien ts wi th al ler gic di sea ses de mon stra tes et hnic and gen der va ria bi li ty (21).…”