RESUMO
A short historical review of the antimicrobial effects of siderophilin, the iron chelator in human plasma and serum, is followed by a presentation of the rational basis for assigning it a role in the overall defence mechanisms of the host against infectious disease. Details are given of the qualitative and quantitative activities of normal and pathological sera on the growth and nutrition of several pathogenic bacteria and the fungus Candida albicans as governed by the percentage iron saturation of their contained siderophilin. Staphylococcus aureus is differentiated from Staphylococcus albus by its ability to grow in normal serum whose percentage iron saturation affects not only the metabolism of Staphylococcus aureus but also its production of diffusible factors and sensitivity to antibiotics. The protein iron chelator of bodily secretions, ekkrinosiderophilin, found in relatively high concentrations in human milk is likewise evaluated for its antimicrobial properties and their relevance to the health of the newborn.
Assuntos
Anti-Infecciosos , Lactoferrina/farmacologia , Lactoglobulinas/farmacologia , Transferrina/farmacologia , Antibacterianos/farmacologia , Antifúngicos , Candida albicans/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Feminino , Humanos , Ferro/sangue , Lactoferrina/análise , Lactoferrina/metabolismo , Masculino , Leite Humano/análise , Especificidade da Espécie , Staphylococcus/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Transferrina/análise , Transferrina/metabolismoAssuntos
Candida/efeitos dos fármacos , Candidíase Cutânea/imunologia , Ferro/farmacologia , Lactoglobulinas/farmacologia , Líquidos Corporais/análise , Líquidos Corporais/imunologia , Candida albicans/efeitos dos fármacos , Candidíase Cutânea/sangue , Candidíase Cutânea/metabolismo , Núcleo Celular/metabolismo , Doença Crônica , Imunofluorescência , Humanos , Imunoeletroforese , Ferro/metabolismo , Lactoglobulinas/análise , Lactoglobulinas/sangue , Leucócitos/análise , Leucócitos/imunologia , Neutrófilos/análise , Glândula Parótida/metabolismoRESUMO
1. A protein, aggregating at body temperature and solubilizing when cooled, was isolated from fresh human milk at neutral pH and studied for some of its physical, chemical and immunological properties. The name ;galactothermin' is proposed for this protein. 2. Isolation and purification of galactothermin involved casein removal from skim milk at pH4.64 followed by centrifugal fractionation of residual protein-containing solutions repeatedly heated and cooled between 40 degrees C and 0 degrees C at pH7.3. 3. The molecular weight by ultracentrifugal analysis and the minimum molecular weight by sum of amino acid residues were 11400 and 14000 respectively. The sedimentation coefficient s(25,w) was 1.05S and the diffusion coefficient was 7.15x10(-7). Reversible aggregation is favoured by increase in protein concentration, ionic strength, temperature, time and approach to the isoionic point of 7.27 from either acidic or alkaline conditions. 4. Among the amino acid residues, proline predominates and non-polar species account for two-thirds of the total. Cysteine and cystine are absent. Analysis of galactothermin showed it to be essentially free of hexose, sialic acid, calcium and phosphate. 5. Galactothermin is antigenic in the rabbit as evidenced by the passive cutaneous anaphylaxis test. Single precipitin lines are produced in immunodiffusion tests. 6. By electrophoresis in polyacrylamide gel at pH4.0 only one sharp band is produced.