Influence of MHC Background on the Antibody Response to Detergent Enzymes in the Mouse Intranasal Test
| Autor: | Jennifer S. Parris, Patricia A. Horn, Edwin D. Clark, Katherine Sarlo, J. Ann McCay, Michael K. Robinson, Vanessa L. Peachee, Kimber L. White, Yvonne L. Veloso |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Proteases
medicine.medical_treatment Detergents Congenic Biology Toxicology Immunoglobulin E Major histocompatibility complex Major Histocompatibility Complex Rats Sprague-Dawley Mice Immune system Inbred strain Hypersensitivity medicine Animals Subtilisins Administration Intranasal chemistry.chemical_classification Protease Serine Endopeptidases H-2 Antigens Molecular biology Rats Mice Inbred C57BL Enzyme chemistry Mice Inbred DBA Immunoglobulin G Antibody Formation Models Animal Immunology biology.protein Female |
| Zdroj: | Toxicological Sciences. 58:299-305 |
| ISSN: | 1096-0929 |
| Popis: | b/d ), a cross of C57Bl/6 (H-2 b ) 3 DBA/2 (H-2 d ) has been used for most of the development work. Preliminary data in the CB6F1(H-2 d/b ), a cross of Balb/c (H-2 d ) 3 C57Bl/6 showed that this strain was similar to the BDF1 in its response to enzymes. These data also showed that the parental strains responded differently to the enzymes. To understand better the influence the major histocompatibility complex (MHC) background has on immune responses to enzymes, 3 different enzymes were tested in 4 inbred strains (C57Bl/6, DBA/2, Balb/c, and C57Bl/10), 2 hybrid strains (BDF1 and CB6F1), and 2 congenic strains (Balb.B10 and B10.D2). BDF1 mice rank enzymes the same as the guinea pig, which in turn correlates with sensitization in occupationally exposed humans. The ranking is based upon the dose of enzyme needed to give one-half maximal IgG1 antibody response (ED50) where Termamyl is more potent than Alcalase, which is equipotent to Savinase. The H-2 d strains ranked the enzymes the same as the BDF1 but generated ED50s for the proteases that were one order of magnitude greater than the BDF1 ED50s. The response to Termamyl was the same in the two F1 strains and the H-2 d strains. The H-2 b strains did not rank the enzymes the same as BDF1 but the ED50s for the proteases were similar to the ED50s in the F1 strains. The response to Termamyl in the H-2 b strains was lower than the response in the F1 and H-2 d strains. Initial data show that the inbred strains will make enzyme-specific IgE antibody to high doses of enzyme with DBA/2 > Balb/c > C57Bl/6 in terms of the robustness of the response. The IgG1 responses in the congenic strains were similar to the responses in the H-2 matched strains. In addition, the antibody response to enzymes was consistent regardless of the source of BDF1 mice. The responses to these enzymes are clearly MHC linked with a role for Class II I-E molecules indicated. The current data strongly support the use of the F1 hybrid as an appropriate strain for evaluating allergic responses to enzymes. Occupational IgE antibody-mediated allergic responses and asthma to enzymes used in the detergent industry were first described by Flindt (1969) and Pepys et al. (1969). These reactions were noted shortly after the start of extensive manufacture of enzyme-containing detergents (Newhouse et.al., 1970; Greenberg et al., 1970; Shapiro and Eisenberg, 1971). As a result, enzyme manufacturers developed less dusty enzymes and the industry instituted extensive dust control measures and exposure guidelines. The incidence of allergic responses and occupational asthma caused by detergent enzymes is now a rare event (Juniper and Roberts, 1984; Flood et.al., 1985; Sarlo et al., 1990; Schweigert et al., 2000). A guinea pig intratracheal (GPIT) test was developed to assess the relative allergenic potential of new enzymes when compared to a reference protease, Alcalase (Ritz et al., 1993). This enzyme was chosen as the reference since the bulk of our human experience has been with this protease and the ACGIH established a threshold limit value of 60 ng pure protein/m 3 |
| Databáze: | OpenAIRE |
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