Erican Society for Microbiology. All Rights Reserved.Vol. 73, No.Chitinase and Fizz Family Members Are a Generalized Function of Nematode Infection with Selective Upregulation of Ym1 and Fizz1 by Antigen-Presenting CellsMeera G. Nair,1 Iain J. Gallagher,1 Matthew D. Taylor,1 P’ng Loke,2 Patricia S. Coulson,3 R. A. Wilson,3 Rick M. Maizels,1 and Judith E. Allen1Ashworth Laboratories, University of Edinburgh, Edinburgh,1 and Department of Biology, University of York, York,3 United kingdom, and Howard Hughes Health-related Institute, University of California, Berkeley, CaliforniaReceived 3 June 2004/Returned for modification 14 July 2004/Accepted ten SeptemberYm1 and Fizz1 are secreted proteins which have been identified in a selection of Th2-mediated inflammatory settings. We initially found Ym1 and Fizz1 as extremely expressed macrophage genes inside a Brugia malayi infection model. Right here, we show that their expression is Fc Receptor-Like Proteins Gene ID really a generalized feature of nematode infection and that they’re induced in the web site of infection with each the tissue nematode Litomosoides sigmodontis plus the gastrointestinal nematode Nippostrongylus brasiliensis. At the Protein Tyrosine Kinases Proteins supplier web-sites of infection with N. brasiliensis, we also observed induction of other chitinase and Fizz family members members (ChaFFs): acidic mammalian chitinase (AMCase) and Fizz2. The higher expression of both Ym1 and AMCase inside the lungs of infected mice suggests that abundant chitinase production is an crucial feature of Th2 immune responses within the lung. Additionally to expression of ChaFFs inside the tissues, Ym1 and Fizz1 expression was observed within the lymph nodes. Expression each in vitro and in vivo was restricted to antigen-presenting cells, together with the highest expression in B cells and macrophages. ChaFFs may well hence be essential effector or wound-repair molecules in the web-site of nematode infection, with prospective regulatory roles for Ym1 and Fizz1 inside the draining lymph nodes. Macrophages are a fundamental feature of chronically inflamed tissue. Inside the course of long-term inflammation, the macrophage phenotype normally shifts away from a extremely microbicidal state towards an “alternative activation” pathway because the T-cell cytokine profile shifts from form 1 to type two (16). Within the case of helminth infection or allergy, the sort 2 response can dominate from the outset. Though our understanding of macrophage activation under these kind two situations is growing, whether or not macrophages market the disease state or safeguard against it remains essentially unknown. We and other folks have lately found that macrophages activated by form two cytokines in vivo create higher levels of two secreted proteins, Ym1 (9, 12, 51) and Fizz1 (31, 36, 40). Inside a nematode infection model, we discovered that Ym1 represents more than ten on the total nematode-elicited macrophage (NeM) mRNA, even though Fizz1 will be the second most abundant transcript at 2 (31). Ym1 is often a member of a household of mammalian proteins that share homology to chitinases of lower organisms (25). Despite the fact that Ym1 was originally described as an eosinophil chemotactic element (38, 39), the dramatic level of production by macrophages and its capacity to bind chitin and connected glycan structures (9, 46) recommend that eosinophil chemotaxis, a home that remains controversial (9), isn’t its principal function. Ym1 might have a defensive role by binding fungal or other pathogens containing chitin, but obtaining no apparent chitinase activity, its effector mechanisms stay unclear. These mechanisms may include the sequestration.
