Control of the first‐line human defence system An autocatalytic model

Abstract

If you would like to write for this, or any other Emerald publication, then please use our Emerald for Authors service information about how to choose which publication to write for and submission guidelines are available for all. Please visit www.emeraldinsight.com/authors for more information. About Emerald www.emeraldinsight.comEmerald is a global publisher linking research and practice to the benefit of society. The company manages a portfolio of more than 290 journals and over 2,350 books and book series volumes, as well as providing an extensive range of online products and additional customer resources and services.Emerald is both COUNTER 4 and TRANSFER compliant. The organization is a partner of the Committee on Publication Ethics (COPE) and also works with Portico and the LOCKSS initiative for digital archive preservation.Abstract A control of the first-line human defence system, using mechanisms analogous to specific and non-specific (parametric) triggering of phagocytosis, is proposed on the basis of an autocatalytic model of biphasic modulation of phagocyte luminescence by experimental peptide medicines. Properties of the autocatalytic model are described and its catastrophe and bifurcation sets determined. The mechanism analogous to parametric triggering is shown to result from a fold catastrophe produced by the changes in the autocatalytic interaction parameter characterising a given peptide preparation. Usefulness of the model was shown by its application to two distinct peptide preparations having different immunomodulatory properties.

Kinetics of the biphasic modulation of phagocytosis

“…As shown in (Kochel, 1999) the biphasic modulation of phagocytosis was found to be described by the following autocatalytic process:…”

“…Only the topological-differential type of the CPC(c) function is important from the viewpoint of regulation of a phagocytic activity of neutrophils (Kochel, 1999), therefore concrete values of the parameters in equation 1 have no meaning. Consequently, the CPC(c) function can be described by sets of different values of the parameters occurring in it.…”

“…CPC is a measure of inhibition of phagocytosis and directly proportional to the reduction of chemiluminescence. From the definition (Kochel, 1992(Kochel, , 1999, CPC is inversely proportional to the mean value of the relative reaction rate of perturbed neutrophils against native ones, therefore it ± as a quantity unequivocally related to the reaction rate ± can be used in a construction of kinetic models. Positive values of CPC, corresponding to inhibition of phagocytosis, are the consequence of the reduction of reactive oxygen species (ROSs) through either a scavenging or a reduced generation of ROSs.…”

“…Since the experimental discovery of biphasic modulation of a phagocytic activity of human neutrophils by the peptide preparation Immax A 1 (Kochel, 1996) a biochemical kinetic model and corresponding mechanisms underlying this phenomenon have not been known. In this paper such a model was constructed on the basis of the feedback loop-containing (autocatalytic) process which had been developed by the use of biocybernetic notions and inferences (Kochel, 1999). Because neither pro-nor anti-phagocytic properties of Immax A 1 have been known so far no starting suggestions on reaction mechanisms were possible while the kinetic model was constructed.…”

“…The experimental dependence of the integrated luminescence-based measure of inhibition of phagocytosis upon the concentration of Immax A 1 (Kochel, 1999) and the fact that the bacterial N-formyl peptide fMet-Leu-Phe (fMLP) was digested in vitro by neutrophils were the only directions. All of the assumptions about the reactions of neutrophils which had to be taken into account while a biochemical-valued kinetic model was built must be in accordance with known properties of human neutrophils and with the notions and rules of biochemistry of peptide ligand-binding reactions.…”