Student Theses and Dissertations

Date of Award

1991

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Abstract

Polymorphonuclear leukocytes (PMN) express a receptor of the integrin family termed complement receptor type 3 (CR3, also known as ocMp2, Mac-1, Mol, or CDllb/CD18) that functions in several cell-cell and cell-substratum adhesion events. The capacity of CR3 to mediate adhesion may be rapidly and reversibly enhanced without changes in the number of receptors expressed on the cell surface. This thesis describes an acidic, amphiphilic lipid, termed integrin modulating factor (IMF-1), that may serve to control CR3 avidity. Addition of IMF-1 to cells or to purified CR3 causes enhanced binding of ligand. IMF-1 cannot be extracted from resting PMN but can be extracted from cells within one minute of stimulation with a variety of agonists (PMA, TNF, formylated peptides, platelet activating factor). The amount of IMF-1 extracted declines to low levels within an hour of continued stimulation. The time course of IMF-1 extraction corresponds precisely with the transient increase in the adhesive activity of CR3 observed in PMN stimulated with these agonists. IMF-1 can also increase the binding activity of another leukocyte integrin, LFA-1 (αLβ2, CD1WCD18). However, IMF-1 does not affect the function of representative β1 and β3 integrins. IMF-1 has a molecular weight of 340 + 16 daltons by size exclusion chromatography and appears to be distinct from the known lipid products of PMN. The data suggest that PMN control their adhesivity through a novel lipid that may act as an allosteric activator of leukocyte integrins.

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