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Demonstration of a macrophage migration enhancement factor in the sera of young rabbits
Abstract:
Alveolar macrophages (AM), harvested from the lungs of untreated normal young rabbits (New Zealand White) 14 days to 8 weeks of age, exhibited a state of migration stimulation compared to AM from normal adult rabbits (5 to 6 months of age). Migration of AM from normal adult rabbits (New Zealand White) was stimulated 2.0- to 2.5-fold when incubated with sera from 39- to 46-day-old rabbits compared with sera from normal adult rabbits. Furthermore, 4-day spleen cultures obtained from animals 28 to 59 days of age yielded supernatants that also stimulated the migration of adult AM. The spleen cell culture supernatants from 42- to 49-day-old animals had the greatest activity and stimulated the migration of adult AM 2.5- to 3.2-fold compared to the supernatants from adult normal rabbits. The peak production of migration enhancement factor (MEF) by splenic lymphoid cells coincided with the peak activities found in the sera. It was observed that nonadherent peanut agglutinable lymphoid cells produced MEF. When sera or culture supernatants containing MEF were mixed with MIF-containing adult sera or spleen cell culture supernatants, the respective activities were neutralized. The large migrations of normal neonatal AM were diminished by the addition of MIF-containing sera obtained from BCG-sensitized/challenged rabbits. In contrast, AM from BCG-sensitized rabbits, which exhibited a state of reduced migration, were enhanced by MEF-containing sera from untreated young rabbits. Three peaks of MEF activity were detected in Sephadex G-100 column fractionated sera from 42-day-old rabbits having MWs of approximately (Peak I) 80,000, (Peak II) 43,000, and (Peak III) 8000 to 18,000; most of the activity was found in peaks II and III. Two peaks of MEF activity were detected in Sephadex G-100 column-fractionated spleen cell culture supernatants from 42-day-old rabbits having MWs of approximately (Peak I) 35,000 to 43,000 and (Peak II) 10,000 to 14,000; most of the activity was in peak I which corresponds to peak II of the serum fractionation experiment. Collectively, these data indicate that MEF is a lymphokine that could be important in the modulation of cell-mediated immune effector responses.
Insights
Young rabbit sera and spleen cell supernatants contain a migration enhancement factor (MEF) that stimulates alveolar macrophage migration. This lymphokine, MEF, plays a role in modulating immune responses and its activity is distinct from migration inhibitory factor (MIF).
Area of Science:
- Immunology
- Cell Biology
Background:
- Alveolar macrophages (AM) play a crucial role in lung immunity.
- The regulation of AM migration is critical for effective immune responses.
- Factors influencing AM migration in young versus adult animals are not fully understood.
Purpose of the Study:
- To investigate the presence and characteristics of factors that enhance alveolar macrophage migration in young rabbits.
- To determine if these factors are produced by splenic lymphoid cells and present in sera.
- To explore the relationship between migration enhancement factor (MEF) and migration inhibitory factor (MIF).
Main Methods:
- Harvesting alveolar macrophages from young and adult New Zealand White rabbits.
- Incubating AM with sera and spleen cell culture supernatants from rabbits of different ages.
- Stimulating AM migration and quantifying the fold-increase.
- Utilizing Sephadex G-100 column fractionation to determine molecular weights of active factors.
- Investigating the interaction between MEF and MIF through neutralization experiments.
Main Results:
- Sera and spleen cell supernatants from young rabbits significantly stimulated adult AM migration.
- Peak activity of migration enhancement factor (MEF) was observed in sera and supernatants from 42- to 49-day-old rabbits.
- MEF activity was associated with nonadherent, peanut agglutinable lymphoid cells.
- MEF activity was distinct from and not neutralized by MIF.
- Fractionation revealed MEF with molecular weights of approximately 80,000, 43,000, and 8000–18,000 in sera, and 35,000–43,000 and 10,000–14,000 in supernatants.
Conclusions:
- A lymphokine, designated migration enhancement factor (MEF), is present in young rabbit sera and spleen cell supernatants.
- MEF enhances the migration of alveolar macrophages.
- MEF plays a role in modulating cell-mediated immune effector responses.
- MEF activity is distinct from MIF and its production by splenic lymphoid cells suggests a role in early immune development or response.