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Production of leucocyte inhibitory factor (LIF) and macrophage inhibitory factor (MIF) by PHA-stimulated lymphocytes
Abstract:
Supernatants from human mononuclear cells cultured with PHA inhibited the migration of both human polymorphonuclear leucocytes and guinea-pig peritoneal exudate cells, but not human mononuclear cells. Using ultrafiltration it was shown that these supernatants contained two inhibiting factors, the one with a molecular weight of 15,000-50,000 inhibited only guinea-pig peritoneal exudate cells (MIF), whereas the fraction containing molecules of a size between 50,000 and 75,000 specifically inhibited the migration of polymorphonuclear leucocytes (LIF). The polymorphonuclear leucocyte inhibiting activity was heat labile. It is suggested that the leucocyte migration inhibition test is dependent upon the production of a lymphokine (LIF) which acts specifically on polymorphonuclear leucocytes causing their inhibition of migration.
Insights
Researchers identified two factors in human cell cultures that inhibit immune cell migration. One factor specifically affects polymorphonuclear leucocytes (LIF), suggesting its role in the leucocyte migration inhibition test.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human mononuclear cells, when cultured with phytohemagglutinin (PHA), release factors that modulate immune cell behavior.
- Previous studies indicated that cell-free supernatants can influence leucocyte migration patterns.
Purpose of the Study:
- To identify and characterize the factors present in PHA-stimulated human mononuclear cell supernatants that inhibit leucocyte migration.
- To determine the specificity of these inhibitory factors on different types of leucocytes.
Main Methods:
- Ultrafiltration was employed to separate inhibitory factors based on molecular weight.
- Migration inhibition assays were performed using human polymorphonuclear leucocytes, human mononuclear cells, and guinea-pig peritoneal exudate cells.
Main Results:
- Supernatants inhibited the migration of human polymorphonuclear leucocytes and guinea-pig peritoneal exudate cells, but not human mononuclear cells.
- Two distinct inhibitory factors were identified: one (15,000-50,000 MW) inhibited guinea-pig cells (macrophage migration inhibitory factor - MIF), and another (50,000-75,000 MW) specifically inhibited human polymorphonuclear leucocytes (leucocyte migration inhibitory factor - LIF).
- The LIF activity was found to be heat labile.
Conclusions:
- The leucocyte migration inhibition test may rely on the production of LIF, a lymphokine that specifically inhibits polymorphonuclear leucocyte migration.
- These findings contribute to understanding the mechanisms of cell-mediated immunity and the function of specific lymphokines.