Calgranulin C Has Filariacidal and Filariastatic Activity

Abstract

The calgranulins are a family of calcium- and zinc-binding proteins produced by neutrophils, monocytes, and other cells. Calgranulins are released during inflammatory responses and have antimicrobial activity. Recently, one of the calgranulins, human calgranulin C (CaGC), has been implicated as an important component of the host responses that limit the parasite burden during filarial nematode infections. The goal of this work was to test the hypothesis that human CaGC has biologic activity against filarial parasites. Brugia malayi microfilariae and adults were exposed in vitro to 0.75 to 100 nM recombinant human CaGC. Recombinant CaGC affected adult and larval parasites in a dose-dependent fashion. Microfilariae were more sensitive to the action of CaGC than were adult parasites. At high levels, CaGC was both macrofilariacidal and microfilariacidal. At lower levels, the percentage of parasites killed was dependent on the level of CaGC in the culture system. The larvae not killed had limited motility. The filariastatic effect of low-level CaGC was reversed when the CaGC was removed from the culture system. Immunohistochemical analysis demonstrated that human CaGC accumulated in the cells of the hypodermis-lateral chord of adult and larval parasites. The antifilarial activity of CaGC was not due to the sequestration of zinc. Thus, the cellular and molecular mechanisms that result in the production and release of CaGC in humans may play a key role in the regulation of filarial parasite numbers.

Differential proteomic analysis reveals increased cathelicidin expression in porcine bronchoalveolar lavage fluid after an Actinobacillus pleuropneumoniae infection

“…The antibacterial properties of the amino terminal 60 residues of prophenin-1, primarily directed against gram negative organisms, have long been known [18,23], and recently it has been shown that, even in the presence of a lung surfactant preparation, an 18-residue carboxy terminal fragment also possesses antibacterial activity [9,35]. Calgranulin C belongs to a family of calcium-and zinc-binding proteins and also possesses antimicrobial as well as filariacidal activity [16]. Because PR-39 has been reported to be increased in serum after infection [39] and, because this antimicrobial peptide is involved in wound repair processes [12], we hypothesised that PR-39 might be an appropriate disease marker in BALF facilitating the detection of convalescent animals, which still might be carriers of the pathogen.…”

Insight into the host–parasite interplay by proteomic study of host proteins copurified with the human parasite, Schistosoma japonicum

“…Another secreted protein, CS-VI, also termed as neutrophil antibiotic peptide NP-6 [30], was found in the egg samples. Calgranulin C, another antimicrobial protein, was reported to be secreted by activated neutrophils onto the worm surface of Onchocerca volvulus for eliciting the antifilarial effect [31,32]. The antimicrobial protein CAP18, an essential component of the mammalian innate immune system [33,34], were also found in the egg samples.…”

“…Host DJ-1, a molecule playing a role in antioxidative stress by eliminating reactive oxygen species [46], is also helpful for schistosome eggs when evading host's attacks. The most abundant host protein found in the adult worm sample of S. japonicum is a proteinase inhibitor, Serpin A 3K (30 MS/MS, combined MASCOT score, 2169, Table 2 and Supplementary Table 3), by which the schistosome may counteract or attenuate toxic enzymes such as elastase released by host neutrophils [31,32]. Another host proteinase inhibitor, Serpin A 3M, was also found in adult worm sample.…”

The expression of RAGE and EN-RAGE in leprosy

“…This suggests that EN-RAGE may not suppress the survival of M. leprae, unlike the report indicating that EN-RAGE has a filaricidal effect on Brugia malayi in vitro. 30 EN-RAGE may be induced by M. leprae per se or its wall components; subsequently, TNF-a is released by inflammatory cells infiltrated in MB leprosy lesions, which, in turn, may induce EN-RAGE expression.…”