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Biomedical subjects

A B Kay

Publications and source records attributed to A B Kay.

At least 415 records · Page 23Linked to original sources

A prealbumin activator of prekallikrein. 3. Appearance of chemotactic activity for human neutrophils by the conversion of human prekallikrein to kallikrein.

Human plasma kallikrein has been shown to directly and selectively attract human neutrophils from a mixed leukocyte population. The capacity of plasma kallikrein to be chemotactic and to generate the nonapeptide bradykinin was maintained during progressive purification. While neither highly purified prekallikrein nor the prealbumin Hageman factor fragments were chemotactic alone, their interaction so as to convert prekallikrein to kallikrein yielded both chemotactic and kinin-generating activity. Both functions of kallikrein were inhibited by treatment with diisopropyl fluorophosphate, indicating an essential role for the active site of the enzyme in the expression of its chemotactic activity.

Binding Sites↗

An eosinophil leukocyte chemotactic factor of anaphylaxis.

The capacity of actively or passively sensitized guinea pig lung to react with antigen to release a factor specifically chemotactic for eosinophil leukocytes (ECF-A) has been demonstrated. The release of ECF-A was also accompanied by the elaboration of both histamine and SRS-A and the appearance of all these mediators exhibited a similar response in terms of the time course of passve sensitization, the effect of antigen dose, the time course of release, divalent cation dependence and enhancement by the presence of succinate or maleate. Decomplementation by the administration of purified cobra venom factor had no effect on the antigen-induced release of ECF-A from actively or passively sensitized lung fragments. When fragments of guinea pig lung were passively sensitized with fractions of guinea pig 7S IgG, only the IgG(1)-containing fractions prepared tissue for the antigen-induced release of ECF-A. Histamine, SRS-A, bradykinin, serotonin, and the prostaglandins PGE(1), PGE(2), and PGF(2alpha) were not eosinophilotactic per se; neither was ECF-A detected following the incubation of these agents with sensitized lung in the absence of antigen. Both eosinophilotactic activity and SRS-A survived extraction in 80% ethanol and evaporation to dryness. SRS-A, however, withstood boiling in alkaline solution for 20 min, whereas ECF-A activity was abolished by this procedure. SRS-A and ECF-A could also be separated by gel filtration. ECF-A activity was completely recovered following its passage through a column of Sephadex G-25 and had an estimated molecular weight of between 500 and 1000. On the basis of size and a formation mechanism independent of the complement system, ECF-A is distinguishable from a previously described complement-dependent eosinophilotactic factor (ECF-C). Thus, ECF-A represents a hitherto undescribed agent which selectively attracts eosinophil leukocytes.

Anaphylaxis↗

Activated human eosinophils generate SRS-A leukotrienes following IgG-dependent stimulation.

Eosinophils, a class of granular leukocytes, are prominent in many inflammatory processes, particularly in asthma, certain allergic diseases and during infections with helminthic parasites. Following incubation with the Ca ionophore A23187 (refs 1-4) (a non-physiological agent which circumvents membrane calcium-gating mechanisms), eosinophils generate large amounts of sulphidopeptide leukotrienes, potent inducers of smooth muscle constriction and mucus production. These are now known to represent the activity previously termed 'slow-reacting substance of anaphylaxis' (SRS-A) but attempts to identify a physiological stimulus for SRS-A production by eosinophils have so far been unsuccessful. The cells contain recognized receptors for IgG (Fc) and it is known that they adhere to, and can be activated by, contact with the surface of large organisms such as helminthic larvae. We show here that eosinophils, particularly when activated, produce sulphidopeptide leukotrienes after contact with large particles coated with IgG.

Eosinophilia↗