Dear Rakesh,

The endotoxin detoxification mechanisms are review in: Detoxifying endotoxin: time, place and person by Robert S. Munford, Journal of Endotoxin Research, Vol. 11, No. 2, 2005.

As Blake said the mechnism depend on the toxin and is variable berween individuals.

In response to your question, phagocytes are involved in these processes through, for example: proteins produced by neutrophils (BPI, lactoferrin, lysozyme) or PRR.

Hello Rakesh,

Monocytes/macrophages can play a a dual function in the body.

Monocytes, activated by microorganisms or their parts, certain pro-inflammatory cytokines (e.g. IFN-γ), GM-CSF, and M-CSF, migrate into tissues and differentiate into proinflammatory cells, referred to as MI macrophages. This cells are involved in the destruction of microorganisms and neoplastic cells, among others.

Monocytes activated by such factors as IL-4, IL-13, IL-10, and M-CSF show typical activities of anti-inflammatory cells; when present in tissues, they are referred to as MII macrophages. The principal tasks of MII include the suppression of adaptive response, inhibition of cytotoxic cell activity, rearrangement and reconstruction of destroyed tissues, and their neovascularization. MII macrophages exert several pro-tumoral functions as well.

A lot of interesting information regarding Macrophages can be found in the review paper "The chemokine system in diverse forms of macrophage activation and polarization" Trends in immunology Volume 25, Issue 12, December 2004, Pages 677–686

Dear Rodrigo,

Thanks! Does inflammation favour host or pathogen more?

Dear Andrzrej,

Thanks! Can activated leukocytes detoxify the bacterial toxins sans microbes? If yes then how e. g. endotoxin, lytic enzymes etc?

I am not able to open the your article you have mentioned in order to understand your question.

Inflammation is designed to defend the host (interestingly, sometimes to the very cost of its life). However, there are many aspects involved, as it is a very complex mechanism; germs that have co-evoluted with the human species (like Mycobacterium tuberculosis) have developed ways to modulate and even survive to the immunity in some cases. Some examples of the complexities involved:

- some proinflammatory signals, like IL-1, are so powerful that their incontrolled effect can result harmful for the body itself. IL-1 is actually a system of 2 molecules - one is active, the other is inhibitory. They connect with 2 existing receptors: one activates the metabolic pathways, the other is a decoy receptor that binds and blocks molecules of IL-1 (I may not be very up to date to more complex newly discovered aspects)

- chronic inflammation results usually in damage to the host (ex.-periodontitis)

- some germs are able to induce and modulate the host's inflammatory response, in order to take advantage of some of its aspects, while can resist to others - the result can be damaging to the host as well in various degrees.

Sabiha: To open this article, please clik first on the given link in question and next click on right side at the box showing first page of the article after entering your ResGate password, as directed by built in program.

Rodrigo: it may mean that if, excessive inflammation interferes with vital functions, then it may be dangerous, otherwise, one may avoid anti-inflammatory drugs during microbial infections of the human host.

Endotoxin or other bacterial fragments are recognized by PRR (pattern recognition receptors) and activate cells of the immune system (e.g. monocytes/macrophages). This results in an increase in their phagocytic activity and significantly enhances the secretion of proinflammatory cytokines such as TNF, IL-6, etc. Production of inflammatory cytokines is essential for the induction of local inflammation. On the other hand, if their production is unbalanced can lead to septic shock.

Great mini review on PRR: Pattern Recognition Receptors: Doubling Up for the Innate Immune Response; The Cell, Volume 111, Issue 7, 27 December 2002, Pages 927–930

Andrzej

Thanks. Question still remains: "Can phagocytes neutralize cell-free toxins themselves arising from pathogens?"

One can say yes, but that may not be the point. As Andrzej said, some toxins may determin the phagocytes (neutrophils) to activate an abnormal inflammation that could become very damaging / life threatening by itself. Or the phagocytes may not be effective enough.

Depends on the toxin.

In some cases the anticorps may represent the main tool for neutralizing the toxin (ex: diphteria, anthrax) - of course, it means that the specific (late response) immunity is involved (the linphocytes B are activated by the antigen presenting phagocytes), so maybe a second infection can be better defeated by antitoxin antibodies. However, exactly this mechanism is used for vaccination in certain cases - if I am not mistaken is the case for diphteria.

Antitoxin sierum containing antibodies is also used as a treatment for some of these toxic infections.

Dear Rakesh,

The endotoxin detoxification mechanisms are review in: Detoxifying endotoxin: time, place and person by Robert S. Munford, Journal of Endotoxin Research, Vol. 11, No. 2, 2005.

As Blake said the mechnism depend on the toxin and is variable berween individuals.

In response to your question, phagocytes are involved in these processes through, for example: proteins produced by neutrophils (BPI, lactoferrin, lysozyme) or PRR.

Hi Rakesh

As I understood you're looking for role of phagocytic cells to combat toxins of pathogenic organisms. Actually in this regards, antibodies are produced to neutralize any toxins in the body! Therefore B cells are in charge of deal with this agents and macrophages and neutrophils can help antibodies production by providing appropriate cytokine like IFN-gamma from MQs which helps to produce the IgG. Also phagocytic cells as APCs (antigen presenting cells) can present the antigens to T lymphocytes but it is mostly used for structural antigens from microorganisms and toxins are soluble antigens which need antibodies.

Hope it has your response.

Good luck