Currently, the biological activity of peptides participating in the innate immune response is subject
to active studies. Despite primarily described antimicrobial effects of these peptides, the current evidence
shows that these compounds are multifunctional and participate in the interplay between nervous and immune
systems. Some antimicrobial peptides (AMPs), such as α-defensins, are known to bind the melanocortin
receptors (MCRs) on adrenal cells and inhibit the activity of adrenocorticotropic hormone (ACTH), thus
reducing production of ACTH-mediated corticosteroids. These peptides have been called ‘corticostatins’ due
to this effect. Another group of peptides – β-defensins, have also been shown highly-affine binding to MCRs
on melanocytes, thus modulating their functions. Previously, our research has provided the evidence that the
innate immunity peptides may be involved in performance of stress responses and neuroimmune interactions.
However, there is limited information available regarding interactions between AMPs and melanocortin
system. The exact nature of interaction between AMPs and MCRs remains unclear, whereas immune cells
possess these receptors. Only scarce data exist on how AMPs affects the actions of melanocortins when
they bind to these cells. It is also known that AMPs may cause mast cell degranulation, but it has not been
established whether MCRs can participate in performance of these effects. The purpose of this work was to
study the effect of human α-defensins (HNP-1, HNP-4) on the immunomodulatory effects of α-melanocytestimulating hormone (α-MSH). Using ELISA technique, we found that, in the presence of HNP-1 and HNP4, α-MSH-induced inhibition of cytokine interleukin-1 release by human peripheral blood mononuclear cells
in response to lipopolysaccharide in vitro was decreased. The fluorescence microscopy has shown that HNP-1
and HNP-4 abolish the α-MSH-induced suppression of phagocytic activity in cultured human neutrophils.
We have also found that MCR-5 antagonist inhibited histamine release from human mast cells of HMC-1
strain induced by α- and β-defensins. Our findings contribute to clarifying the role of innate immune system
factors in neuroimmune interactions. Further studies on these effects will help us to uncover their molecular
mechanisms.