Local effector functions of capsaicin-sensitive sensory nerve endings : involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1967.tb01984.x

Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin

Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100–200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.

Vitamin C and Immune Function

The action of these two anti-inflammatory agents provides further support for the suggestion that some of their therapeutic effects depend on the inhibition of the production of prostaglandin.

Indomethacin and aspirin abolish prostaglandin release from the spleen.

Prostaglandins are released into the splenic venous blood when the spleen contracts Whatever the significance of this release, the liver and lungs provide an efficient protective mechanism to remove almost all the prostaglandin before it reaches the arterial circulation

Prostaglandins: Their Disappearance from and Release into the Circulation

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1950.tb01004.x

The nature of hepatic and splenic sympathin.

/pdf/bradykinin-and-oedema-formation-in-heated-paws-of-rats-313za85a7q.pdf

Bradykinin and oedema formation in heated paws of rats.

HISTORICAL INTRODUCTION THE first description of tissue mast cells was made in 1877 during an investigation of the staining of fresh tissues by the new aniline dyes then being produced by the German chemical industry. Ehrlichl observed that some cells in the connective tissue of animals contained granules which changed the colour of toluidine blue and certain other dyes as staining proceeded. The numbers of such cells were greater when chronic inflammation or conditions characterised by increased local nutrition were present. For this reason, Ehrlich considered these cells to be overnourished connective tissue elements and called them “Mast cells” (Mastzellen = well-fed cells). In choosing the name of mast cell, he was also influenced by his finding of a high mast cell content in connective tissue subjected to lymph stasis ; as we now know, in the selective lymphatic blockage of elephantiasis, the hypertrophied connective tissue is packed with mast cells and a similar histological picture, though on a smaller scale, is seen in young well-vascularised keloids. Two years after his first discovery, Ehrlich2 found similar cells in the blood, but whereas the blood mast cells, or basophils, take origin in the bone marrow and with the other leucocytes enter the peripheral blood, the more common tissue mast cells are born, live and die in the connective tissue. The similarity in the two kinds of cell lies in their content of watersoluble cytoplasmic granules which have a strong affinity for basic dyes, several of which change colour as staining occurs (metachromasia). Besides discovering and naming the mast cells, Ehrlich also described their morphology, staining properties and distribution, but he then left it to others to elucidate the chemical nature of the granules. But, for the next 60 years, research on this subject remained almost entirely histological and then in 1937 Swedish workers solved one of the riddles of the metachromatic granules of the mast cell. Jorpes and his colleagues in Stockholm had for long been working on the powerful anticoagulant material first isolated from dog liver and hence called heparin. On finding that heparin stained metachromatically with toluidine blue, these workers3 searched the tissues for metachromatism as a possible clue to the site of formation of heparin. And so it was that Jorpes was able to show that there is a good correlation of the mast cell count of a particular tissue and the amount of heparin that can be extracted from it. At that time mast cells were thought to be perivascular in location so as to produce heparin which pours into the blood stream. But a later study of themovement of the perivascular mast cells revealed that they migrate from the blood

Tissue Mast Cells and Tissue Amines

Factors affecting the determination of histidine decarboxylase activity in adult rat tissues have been studied. The optimal conditions vary from tissue to tissue, and the most potent sources of the enzyme are the pyloric part of the stomach, the liver and the duodenum, with less in the kidney. There is no relationship between the histidine decarboxylase activity of a rat tissue and the amount of histamine it contains.

The Formation of Histamine in the Rat

In one colony of Wistar albino rats 23% were resistant to dextran and to egg-white, these animals (non-reactors) failing to show an anaphylactoid reaction after the intraperitoneal or intravenous injection of either of the two substances. Non-reactors were also found in a few other colonies of Wistar rats but not in colonies of other strains. Procedures which potentiated the anaphylactoid reaction in sensitive rats (reactors) did not alter the response of non-reactors. Dextran failed to release histamine from the perfused hind-quarters of non-reactors although other chemical liberators of histamine were effective. Lack of anaphylactoid reaction was not due to a deficiency of skin histamine or 5-hydroxytryptamine, and the blood sugar and serum protein levels of non-reactors were also normal. Non-reactors could be sensitized to antigens and their serum was antigenic to guinea-pigs. It is suggested that non-reactors lack a blood or tissue component with which dextran normally combines to produce an intermediate substance active in releasing amines.

/pdf/rats-resistant-to-the-dextran-anaphylactoid-reaction-4ecfnm8s0i.pdf

G. B. West

Papers

The nature of hepatic and splenic sympathin.

Bradykinin and oedema formation in heated paws of rats.

Tissue Mast Cells and Tissue Amines

The Formation of Histamine in the Rat

Rats resistant to the dextran anaphylactoid reaction