Lakhtin M.V., Afanasiev S.S., Lakhtin V.M., Aleshkin V.A.
G.N. Gabrichevsky Research Institute for Epidemology & Microbiology,
Russia.
ORGAN TYPE FUNCTIONING OF MUCOSAL OPENED CAVITIES OF
ORGANISM
Resume. On the basis of own data conception
and its general positions of functioning
of mucosal opened cavities of organism as mucosal organ were proposed. Conception
and strategies based on it can be useful for development of bioconstructions in medical biotechnology as
well as for prognostic and diagnostic goals in medical microbiology.
Key words: mucosal organ, mucosal barrier, biotope, microbiocenosis, glycoconjugates, recognition, antimicrobials, synbiotic system.
The functioning of mucosal opened
cavities of organism as its mucosal organ (MO) includes the following general characteristics.
1. Universality of structure-functional organization of mucus,
individuality of biotope mucus, tropism of local mucus, state of locally
changeable mucus in on duty regime. 2. Phenotypes of local MO depend on relationships
between probiotic and relatively pathogenic compartments of biotope. 3. Mucus as MO is characterized by space organization (3D-architectures) of
host cells and microbiocenosis. Such complex organization of MO is programmed by
evolutionary and involutionary mechanisms including biorhythmic
assembling-disassembling (periodical abruption and changing of mucus; inducing
biosynthesis and degradation). 4. MO
reveals itself as multifunctional organ possessed different adaptive network
properties (MO as trapped, delivering, adjuvant, stabilizing, preventive, vaccinating,
therapeutically reacting in replies on stress, opened for cofunctioning to
communications of quorum sensing and cross-talking, tuned/ correcting in
processes of recognition/ isolation/ conservation/ elimination/ prolongation of
protection in regime of retaining/ keeping of functioning of on duty reverse
relationships). 5. Main
structures of MO are ranged as hierarchically synchronized in direct
supervising supported with opposite relationships: MO—Mucosal layer (external, intermediate,
inner)—Cell barrier—Epithelial cell surface—Membrane mucins. It
takes play multilevel regulation of mucosal barrier. 6. MO orders mucosal and cellular barrier for localization, submission, fixation
and inactivation of pathogens, exclusion of distribution of pathogens all over
organism, prevention of cellular transformation of epithelial cells into cancer
cells. 7. It takes play coupled network
revealing of antioxidant, antimicrobial, antiviral and antitumor activities of
MO. 8. Sensitivity of eukaryotic
pathogens (yeast like intermediators between bacterial compositions and
associates of microbiocenosis and tissues of the host biotope) serves one of
important indicators of antitumor potential of MO.
9.
In case of appearance of tumor like cells possessing decreased level of differentiation,
MO functions in accordance of strategy of “reversible compensation” when
changed mucosal surrounding medium and cell decor are rebuilt in direction of
original healthy status (images of normally functioned MO) that prevents
amplification of tumor like cells and further development of tumors. 10. MO serves the library/ catalog/
memory and source of spectra of MGC, as well as diagnostic indicator and sensor
accumulator/ amplifier of tumor antigenic signals. 11. MO is used for delivery, depositing and further release of
therapeutic agents (therapeutic antibodies against tumor antigens, agents of
suppression of other negative biomarkers). 12.
Recognition by mucus and local binding to molecular-cellular targets within MO passes
by natural ways in on duty regime involving participation of super lectin
systems (SLS) involving LS of probiotic microbes and mucin type glycoconjugates
(MGC). Such SLS influence organization (net of pores of regulated size,
permeability) and regulation of functioning MO. 13. SLS (alone or in complexes to MGC) adapt architecture of MO for
delivery of MGC, their retaining and further release by portions (system SLS-MO
as adjuvant). SLS support antipathogenic control within MO. 14. SLS initiate, stabilize, support
and conserve microbiocenoses of healthy status of biotope. 15. Mucosal biotopes of MO function as synbiotic biotopes
(synbiotopes). 16. Diversity of MGC
provides latitude of adaptive replies of MO on stress. The choice of panels of MGC
depends on mucosal biotope type, current healthy status of individual and
diagnosis of patient. 17. On duty network
of SLS-MGC increases potential of MO against viral and other inducers of tumors;
supports MO as source of therapeutic GC and their cascades. 18. MO and its microbiocenosis function
as communicative “bodies” at the level of exchange with signals as well as at
supracellular hierarchic levels involving SLS.
Aforementioned
above conception of MO can be applied for choice adequate strategy against
pathogens, for diagnostics and prognostics in medical microbiology as well as for
bioconstructing in medical biotechnology.
Strategies, tactics, proposals, methodological aspects and
prospects of application of SLS and MGC in respect of functioning MO [1-9, completed].
1. Adequacy
of chosen model system “LS of probiotic bacteria in polyacrylamide gel
[LSPB-PAG]—Mucin glycoconjugates-PA [MGC-PA]” in respect of MO (its mucosal
layer, cell surface mucins and epithelial membranes).
2. It
is of reason to use probiotic combinations of lactobacilli and bifidobacteria
because of lactobacilli stimulate bifidobacteria (the reverse influence is
possible). In addition, LSPB (lectins of lactobacilli and bifidobacteria: LL and
LB) as imitators of probiotic cell activities can be used together with PB
(providing support of balance, resistance and reliability of molecular-cellular
recognition processes in synbiotopes of MO).
2. As a result of delivered
LSPB into biotope, construction LSPB—MO will increase structure-functional
conservation and stability of healthy status of biotope, its resistance to
changes in surroundings (for example, in respect of appearance and
amplification of pathogenic microbes and viruses, àppearance of pathogen-induced tumor like cells,
their associates and tissues).
3. Exogenic delivery of
constructed ”MO based on LSPB“ into
problem biotope will promote exchange MO and altered mucus (as in case of mucus
saturated with MGC from surroundings) and allows redistribution of events to
support healthy status of biotope (for example, vaginal and rectal).
4. MO as directed multipotent affine
architecture under distant control involving chosen complexes LSPB—MGC. Delivery of
construction LSPB—(Chosen panel of GC) into MO will increase not only current
state of biotope but also allow using construction as source of addressed
antimicrobial and antiviral preparations and vaccine ingredients which are based
on participation of MGC. For example, sulfated GC reveal activity against human
immunedeficit virus (HIV) and chitosans (soluble imitators of chitin) as
carriers of therapeutic effectors themselves contribute to sum of antimicrobial
actions.
Construction LSPB—(Chosen
panel of MGC) as supporting biotope will increase synbiotic action of MO and
vary target-dependent effectiveness of delivered therapeutic antibodies (Ab), antigens,
enzymes, antibiotics and bacteriophages into biotope.
5. Other
strategies of using MO are based on non-cellular/ free LSPB. Antimicrobial
strategies of MO using LSPB can include the following dominating synergistic
combinations of lactobacillar and bifidobacterial lectins (LL and BL): a) against pathogenic yeast like fungi (Candida albicans, BL > LL) and
pathogenic Gram positive bacteria (Staphylococcus
aureus, LL > BL); b) anti-C.albicans-cascade
“Acidic BL—Alkaline LL”; c) anti-C.
albicans-combinations of LSPB and phytolectins, BL and azoles. Advantages
of such system combinations are in non-dependence on the presence of PB (PB
need special conditions for supporting their survival including the absence of
a lot of types of antibiotics and other antimicrobials). Disadvantages are inability to use PB-barrier within MO; the lack of biotope uninterrupted
and quick delivery of LSPB produced by
local potential PB.
6. Mutual
cofunctioning of Ab-independent network LSPB—MGC together with on duty complement
system using C3- and C4-subsystems of protection against pathogens (in normal
states and upon systemic diseases).
Conclusion.
Aforementioned conception,
strategies and results indicate importance and reality of prospects of LSPB and
MGC in supporting antipathogenic and antitumor resistance of MO synbiotopes (intestinal, urogenital, others). Some new methodological proposals
to increase mucosal immunity of organism are presented. Conception
underlines the main principles of balanced application of LSPB in
constructing MO resistant
to stress signals Proposed strategies also indicate prospects of development of
MO constructions for therapy of system and other chronic diseases. Conception
and strategies are important for modeling and testing elements/ constituents/ ingredients
of MO. Ïðåäëàãàåìàÿ êîíöåïöèÿ âàæíà äëÿ äàëüíåéøåãî
ðàçâèòèÿ ýêñïåðèìåíòàëüíûõ ïîäõîäîâ ê áèîìåäèöèíñêîé èíæåíåðèè. Super systems LSPB—MGC
reveal universal approach to additional Ab-independed protection in organism.
Such SLS complete known protection systems such as complement, receptor
lectins, cytokines, defensins, others.
References
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Lakhtin M V, Lakhtin V M, Aleshkin V A, Afanasiev S S, Aleshkin A V (2010).
Lectins and enzymes in biology and medicine (in
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bifidobacterial lectins against Candida
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3.
Lakhtin M., Lakhtin V., Aleshkin A., Bajrakova A., Afanasiev S., Aleshkin V.
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8. Lakhtin M.V., Lakhtin V.M.,
Afanasiev S.S., Karaulov
A.V., Bajrakova A.L., Aleshkin V.A., Afanasiev M.S. (2016) Synbiotope – basis against
fungal-bacterial pathogens: New anti-Candida
strategies (in Russian) // Advances in Medical Mycology. 2016. Vol. 15: 243-246.