Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice.

Mucosal surfaces are protected specifically by secretory immunoglobulin A (SIgA) and SIgM generated through external translocation of locally produced dimeric IgA and pentameric IgM. Their active transport is mediated by the epithelial polymeric Ig receptor (pIgR), also called the transmembrane secretory component. Paracellular passive external transfer of systemic and locally produced antibodies also provides mucosal protection, making the biological importance of secretory immunity difficult to assess. Here we report complete lack of active external IgA and IgM translocation in pIgR knockout mice, indicating no redundancy in epithelial transport mechanisms. The knockout mice were of normal size and fertility but had increased serum IgG levels, including antibodies to Escherichia coli, suggesting undue triggering of systemic immunity. Deterioration of their epithelial barrier function in the absence of SIgA (and SIgM) was further attested to by elevated levels of albumin in their saliva and feces, reflecting leakage of serum proteins. Thus, SIgA did not appear to be essential for health under the antigen exposure conditions of these experimental animals. Nevertheless, our results showed that SIgA contributes to maintenance of mucosal homeostasis. Production of SIgA might therefore be a variable in the initiation of human immunopathology such as inflammatory bowel disease or gluten-sensitive enteropathy.

Mice deficient for the complement factor B develop and reproduce normally.

Factor B is an essential component of the complement cascade which forms the C3 and C5 convertase of the alternative pathway. Factor B cleavage products also function as cofactors in antibody-independent monocyte-mediated cytotoxicity, macrophage spreading, plasminogen activation and proliferation of B lymphocytes. Several healthy kindreds heterozygous for the factor B null or non-functional allele have been reported but the absence of homozygous factor B deficiency in humans or in animals has been speculated to be caused by the lethality of the phenotype. Here we report the generation of factor B-deficient mice by gene targeting in vivo. These mice were born at the expected Mendelian ratio and they both develop and breed normally in a conventional animal facility. These mice represent a model of complete alternative pathway deficiency. This model enables the dissection of the complement cascade in vivo and the elucidation of the relative contribution of this complement pathway in the various physiological and pathological phenomena ascribed to the complement system.

Targeted disruption of the murine gene coding for the third complement component (C3).

Complement is a system of more than 30 proteins found both in plasma and on cell membranes. The complement system has several important functions in the immune response including initiation of inflammation, neutralization and elimination of pathogens, regulation of antibody responses, clearance of immune complexes and disruption of cell membranes. Under certain conditions complement may, however, act as a mediator of deleterious inflammatory reactions and complement activation has been implicated in the pathogenesis of autoimmune disorders, atherosclerosis, neurodegenerative diseases, bioincompatibility reactions and decompression sickness. Using gene targeting, we have generated mice deficient for the third complement component (C3). These mice represent an animal model in which complement activation by any pathway is prevented at an early stage. The C3-deficient mice should be valuable for the study of the roles of the complement system in vivo in a variety of physiological and pathological situations.

Accidental deaths from asphyxia. A 10-year retrospective study from Sweden.

Accidental mechanical asphyxia is an unusual cause of death. In reviewing 73 cases occurring during a 10-year-period in Sweden, young boys and elderly women seemed to be most prone to this type of fatality. A striking number of victims had deliberately put a noose-like structure around the neck, and yet another group became entangled in some part of their clothing. Thoracic immobilization was seen in a number of cases, also involving work-related accidents. Hospitalized patients, asphyxiophilics and inebriated victims represent other risk groups. A case involving the use of a helmet is reported in view of the growing frequency with which Swedish children use bicycle helmets. The material contains only a few cases where the victim was not alone at the time of the accident, and it seems plausible that supervision could have prevented many of the reported fatalities. Public knowledge of accident mechanisms may increase the awareness of hazardous situations and activities. Spreading of the medical examiner's knowledge may thus form a basis for accident prevention.