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blood pressure regulation, gastric acid release. Histamine gets activated by binding
with specific receptors of seven transmembrane-spanning receptor families. Four
types of histamine receptors are identified, viz., H 1 R, H 2 R, H 3 R, and H 4 R. The cellular response triggered by histamine depends on the type of receptor it binds with.
Recent findings indicate their role in immune regulation as well.
Histamine binding with HR1 promotes allergic reaction accompanied by the production and secretion of mucus. Histamine triggers hypersensitive reaction. It elicits
enhanced expression of P-selectin. It plays a major role in immune system disorders
as it can regulate many cellular immune system mediators, such as NK cells, T and
B lymphocytes. Monocytes and dendritic cells express all four known histamine
receptors. Histamine activates TH2 cells and immunoglobulin E and thus augments
adaptive immune response. H1R and H2R play an active role in immune regulation.
The antigen-presenting ability of the dendritic cells is potentiated by histamine
binding with H1R and H3R. H1R is found to positively modulate TH1 and TH2
functions and thus amplify immune response. Histamine acting through receptor
HR2 enhances the peripheral antigen tolerance induced by T regulatory (TReg)
cells and thus plays a direct role in regulating cell-mediated immune response.
Histamine docking with H1R contributes to sustained chronic inflammation
leading to rhinitis and asthma. Histamine has been shown to suppress the release of
IL-12 while stimulating that of IL-10 and increasing TH2 response. Moreover, H1R
activation could lead to the release of many proinflammatory mediators, viz.,
colony- stimulating factor, IL-1, IL-6, IL-8, IL-10, IL-11, eotaxin, RANTES, and
tumor necrosis factor (TNF) α, through stimulation of many immunologically active
cells. Histamine via H1R triggers the increased expression of cellular adhesion molecules, including intracellular adhesion molecule (ICAM-1), E-selectin, and
leukocyte- associated antigen, thereby facilitating neutrophil extravasation to the
site of inflammation that further shoots up immune response.
10.2.3 Eicosanoids
These are active fatty acid-based signaling molecules identified with a vital role in
inflammation and immunity and the major eicosanoids include prostaglandins,
prostacyclins, thromboxanes, leukotrienes, and lipoxins (Khanapure et al. 2007).
The members may either augment or reduce inflammatory response. Eicosanoids
are considered as second mediators in the process of inflammation, as their biosynthesis requires prior activation of other mediators like histamine. The release of
phospholipase A2-mediated arachidonic acid (AA) from membrane phospholipids
is the initial step in eicosanoid production. AA undergoes oxidative reactions by
enzymes such as cyclooxygenase (COX) and lipoxygenase (LOX) pathways to generate prostaglandins and leukotrienes respectively. Eicosanoid production is tremendously activated during inflammation.
10 Anti-inflammatory Molecules: Immune System Mediators
blood pressure regulation, gastric acid release. Histamine gets activated by binding
with specific receptors of seven transmembrane-spanning receptor families. Four
types of histamine receptors are identified, viz., H 1 R, H 2 R, H 3 R, and H 4 R. The cellular response triggered by histamine depends on the type of receptor it binds with.
Recent findings indicate their role in immune regulation as well.
Histamine binding with HR1 promotes allergic reaction accompanied by the production and secretion of mucus. Histamine triggers hypersensitive reaction. It elicits
enhanced expression of P-selectin. It plays a major role in immune system disorders
as it can regulate many cellular immune system mediators, such as NK cells, T and
B lymphocytes. Monocytes and dendritic cells express all four known histamine
receptors. Histamine activates TH2 cells and immunoglobulin E and thus augments
adaptive immune response. H1R and H2R play an active role in immune regulation.
The antigen-presenting ability of the dendritic cells is potentiated by histamine
binding with H1R and H3R. H1R is found to positively modulate TH1 and TH2
functions and thus amplify immune response. Histamine acting through receptor
HR2 enhances the peripheral antigen tolerance induced by T regulatory (TReg)
cells and thus plays a direct role in regulating cell-mediated immune response.
Histamine docking with H1R contributes to sustained chronic inflammation
leading to rhinitis and asthma. Histamine has been shown to suppress the release of
IL-12 while stimulating that of IL-10 and increasing TH2 response. Moreover, H1R
activation could lead to the release of many proinflammatory mediators, viz.,
colony- stimulating factor, IL-1, IL-6, IL-8, IL-10, IL-11, eotaxin, RANTES, and
tumor necrosis factor (TNF) α, through stimulation of many immunologically active
cells. Histamine via H1R triggers the increased expression of cellular adhesion molecules, including intracellular adhesion molecule (ICAM-1), E-selectin, and
leukocyte- associated antigen, thereby facilitating neutrophil extravasation to the
site of inflammation that further shoots up immune response.
10.2.3 Eicosanoids
These are active fatty acid-based signaling molecules identified with a vital role in
inflammation and immunity and the major eicosanoids include prostaglandins,
prostacyclins, thromboxanes, leukotrienes, and lipoxins (Khanapure et al. 2007).
The members may either augment or reduce inflammatory response. Eicosanoids
are considered as second mediators in the process of inflammation, as their biosynthesis requires prior activation of other mediators like histamine. The release of
phospholipase A2-mediated arachidonic acid (AA) from membrane phospholipids
is the initial step in eicosanoid production. AA undergoes oxidative reactions by
enzymes such as cyclooxygenase (COX) and lipoxygenase (LOX) pathways to generate prostaglandins and leukotrienes respectively. Eicosanoid production is tremendously activated during inflammation.
10 Anti-inflammatory Molecules: Immune System Mediators