SUMMARYA syslematic study has been carried out lo investigale ihe role of immunoglobulin isotype. cpilope density, and antigen/antibody ratio on the capacity of immune complexes lo activate the classical and alternative pathways of human complement and for the complexes subsequently to bind to erythrocyte C3b-C4b receptors (CRI). For this purpose, a series of chimaeric monoclonal anli-NIP antibodies was used, which all shared ihe same combining site bul had diffcrcnl human constant domains. Antigen epitope density was varied by coupling diftcrent numbers of N IP haplon molecules to bovine serum albumin. All three parameters affect complement fixation. In general, complement activation is better in anlibody excess and at equivalence than it is in anligen excess, and belter al high epitope density Mian at low epitope density, although the ctVccls are variable for different immunoglobulin isolypcs and for the two pathways. It has been confirmed that IgG I and IgG3 are good activators of the classical pathway and are tolerant to variations in bolh epitope density and antigen/antibody ratio. IgG4 and IgA do not activate the classical pathway in any circumstances. IgG2 activates the classical pathway only at high epitope density and al equivalence or antibody excess. IgM aclivates the classical pathway well only at the higher epitope densities and at equivalence orantibodyexcess bul, in addition, shows an inlereslingand unexpected prozonc phenomenon where immune complex in antibody excess inhibits complement activation by the classical pathway. The results ofthe alternative pathway activation are strikingly different. IgA is by far the best activator of the alternative pathway and is relatively tolerant to epitope densily and to antigen/antibody ratio. IgM, IgGi and IgG3 do not significantly activate the alternative pathway in any circumstances. IgG2 is the best IgG subclass for alternative pathway activation but requires high epitope density and equivalence or anlibody excess. Binding to CRI in general parallels the amount of complement lixed independent to the pathway by which it is fixed. However. IgGI and IgG3 complexes in antigen excess activate complement well but bind poorly to CRI. Nascently formed complexes seem to bind complement in a way thai is similar lo thai bound by preformed complexes, but are then less able to bind to red cell CR I. These observations help lo explain the paihogenesis of complement activation in various autoimmune and immune complex diseases such as systemic lupus erythematosus. autoimmune thyroiditis and others.

Lopes RA, Neves KB, Pestana CR, Queiroz AL, Zanotto CZ, Chignalia AZ, Valim YM, Silveira LR, Curti C, Tostes RC. Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria-generated reactive oxygen species involvement.

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Overall, as compared to C, milk biofortification was associated with stabilization of the activity of alternative complement pathway and the neutrophils burst, and modulated different cytokines levels.

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We investigated the capacity of an alkali-insoluble cell wall polysaccharide fraction (FI) ofParacoeeidioides brasiliensis to induce rat polymorphonuclear neutrophil (PMN) migratory and chemiluminescence (CL) responses. Normal rat serum pre-incubated with F1 induced a chemotactic neutrophil response which was fully abolished by heat-inactivation. The participation of the alternative complement pathway was more effective than that of the classical pathway since depletion of factor B by heating at 50°C reduced PMN migration, whereas blockade of the classical pathway with EGTA left the migratory response practically unchanged. Opsonized serum F 1 induced a significant release of oxygen radicals from PMN as measured by CL. The complement system was also found to be involved in this activity since serum inactivation at 56°C altered the CL response. In addition to complementderived fragments, other serum opsonins, probably cross-reacting antibodies, were required for optimal interaction between PM N and opsonized particles. These results contribute to the understanding of the role of fungal components and of the complement system in the inflammatory response observed in paracoccidioidomycosis.Paracoccidioidomycosis or South American blastomycosis is a deep mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis and is the most widespread systemic mycosis in South America [23]. The role of phagocytic cells in the host defense against this fungus is still not well understood. The importance of polymorphonuclear neutrophils (PMN) has been suggested by the finding of a massive infiltration of these cells at the inflammatory sites during the initial stage of the disease in man [12] as well as in experimentally infected animals [3,37]. The presence of PMN has also been detected in the suppurative region of the granulomatous lesions characteristic of the chronic phase of this mycosis [4,11]. A similar inflammatory response was also observed when animals were injected with isolated components of the fungus cell wall such as lipids and polysaccharides [36,37], suggesting that these substances may play an important role in the virulence and pathogenicity of P. brasiliensis. One of these components, the alkali-insoluble polysaccharide fraction (F1),was able to induce accumulation of PMN during the early phase of the inflammatory response in experimental models [3,11]. Furthermore, the F 1 fraction was shown to be able to activate the classical and alternative complement pathways of rats both in vivo and in vitro (L. S. P. Crott, R. T. P. Sobreira, C. L. Silva & J. E. Barbosa, unpublished results).