Inhibition of Chemotaxis by Phospiionate Esters

Fresh normal serum treated with immune complexes is chemotactic for polymorphonudear leukocytes (PMN's) from a variety of species (1, 2). The factor in treated serum causing specific directional migration of PMN's has been identified as a molecular complex consisting of the fifth (C'5), sixth (C~6), and probably seventh (CtT) components of complement (2, 3). The manner by which the chemotactic factor causes migration of leukocytes has proved difficult to analyze and is virtually unknown. The major difficulty in such analysis stems from the obvious requirement for living, intact ceils. Previous work on the antigen-antibody-induced release of histamine from tissue slices and cell suspensions has dearly demonstrated that organophosphorous inkibitors such as diisopropylphosphofluoridate (DFP) and phosphonate esters are particularly suitable for the study of living cell systems (4). These compounds inactivate a specitic group of enzymes, the serine esterases, in a characteristically irreversible manner (5). The p-nitrophenylethyl phosphonate esters have the general structure