A low-molecular-weight eosinophil chemotactic factor (ECF) can be released from human neutrophils on stimulation with the calcium ionophore (A 23187) and during phagocytosis. The presence of human serum suppresses the chemotaxis of eosinophils by ECF significantly. The inhibition is not cell-directed but affects the ECF either by binding or enzymatic cleavage. The inactivators belong to a heterogeneous class of serum components in the 19s, 7s and 4s molecular weight range. Highly purified human IgM and IgA, but neither IgG nor human serum albumin inhibit eosinophil chemotaxis.
The in vivo effectiveness of eosinophil chemotactic factor (ECF), secreted in vitro by human neutrophils (PMN) during phagocytosis, is tested in 2 model systems. Injection of ECF into guinea pig ears causes a preferential attraction of eosinophils with time that is more marked in animals with preexisting eosinophilia. In the same model system, activated serum attracts fewer eosinophils and more PMN. In human skin windows, ECF and activated serum are equally effective on a quantitative basis, but ECF is more selective for eosinophils in patients with eosinophilia. With normal controls, ECF and activated serum attract PMN equally well. The studies confirm previous in vitro observations on the properties of ECF and suggest a potentially significant role of this factor during pathological processes.
Three highly purified serum proteins are examined for their role during leukocyte chemotaxis. In the absence of added proteins, migration of eosinophils towards eosinophil chemotactic factor and of neutrophils towards bacterial factor does not occur at all. Dose-response curves with human serum albumin (HSA) show that chemotaxis proceeds well after addition of HSA, with an optimum at 1 mg/ml. HSA has to be present in the buffer during chemotaxis since preincubation of cells followed by washing is ineffective. In contrast,α2-macroglobulin and α1-antitrypsin enhance leukocyte migration at doses close to physiological serum levels and affect cells irreversibly. The data suggest a complex and powerful modulating influence of serum proteins on the influx of eosinophils and neutrophils to tissue sites.
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