The effect of immunosuppressants on the development of <i>Hymenolepis diminuta</i> in mice

Cortisone, methotrexate and anti-lymphocyte serum were all found to suppress the rejection by SPF CFLP male mice of H. diminuta, which normally occurs between days 9 and 12. Worms continued to grow in mice given immunosuppressants and matured on days 16–18 as they would in a rat, by which time they stretched from the stomach to, and sometimes into, the caecum. Worms in mice given methotrexate ceased to grow after day 16, but this was believed to be due to the deterioration of the host's intestine wall; in mice receiving cortisone growth was faster than normal and worms continued to increase in size until the end of the experiments on days 20–24. The mouse/H. diminuta system is discussed, emphasizing that, as far as is known, H. diminuta (which has no hooks) has no close contact with the tissues and that this is a case of a mammal responding against an organism living freely in the lumen.</jats:p

The role of calcium in the organization of fibrillin microfibrils

AbstractThe microfibrillar glycoprotein fibrillin has a multidomain structure which contains forty-three epidermal growth factor-like motifs with calciumbinding consensus sequences. We have utilized intact microfibrils isolated from human dermal fibroblast cultures to investigate the putative influence of bound calcium on microfibrillar organization and integrity. Incubation with EDTA or EGTA rapidly resulted in gross disruption of microfibril morphology. The treatment induced disorganization of the interbead domains although the regular beaded arrangement was always apparent. These changes were readily reversible on replacing calcium, indicating that the treatment had not compromised microfibrillar integrity. The data localize calcium binding EGF-like repeats to the interbead domains and indicate that lateral packing of fibrillin monomers is calcium-dependent. This arrangement suggests how mutations in epidermal growth factor-like domains of fibrillin might cause the disruption in microfibril organization and interactions which underlies the clinical symptoms of some Marian syndrome patients

Catabolism of intact fibrillin microfibrils by neutrophil elastase, chymotrypsin and trypsin

AbstractWe present ultrastructural and biochemical evidence for the turnover of intact fibrillin microfibrils by the serine proteinases, neutrophil elastase, chymotrypsin and trypsin. Rotary shadowing electron microscopy revealed that serine proteinase treatment of intact microfibrils isolated from foetal bovine skin resulted in extensive degradation. Microfibrils were destroyed by neutrophil elastase and effectively disrupted by chymotrypsin and trypsin, with no morphologically identifiable arrays remaining. Evidence of defined fibrillin degradation products was obtained by Western blotting of these enzyme-treated fibrillin assemblies. Fibrillin immunoprecipitated from dermal fibroblast culture medium was also comprehensively degraded by these enzymes. These observations demonstrate that serine proteinases are potent effectors for the physiological and pathological catabolism of microfibrils, and suggest a key role in elastic fibre degradation