Page 154 - Textbook of Pathology, 6th Edition

138

SECTION I

Figure 6.8 Arachidonic acid metabolites via cyclooxygenase pathway.

predominant enzyme in neutrophils, acts on activated i) Granules of neutrophils. Neutrophils have 3 types of
arachidonic acid to form hydroperoxy eicosatetraenoic acid granules: primary or azurophil, secondary or specific, and
(5-HPETE) which on further peroxidation forms following 2 tertiary.
metabolites (Fig. 6.9): a) Primary or azurophil granules are large azurophil granules
a) 5-HETE (hydroxy compound), an intermediate product, which contain functionally active enzymes. These are
is a potent chemotactic agent for neutrophils. myeloperoxidase, acid hydrolases, acid phosphatase,
b) Leukotrienes (LT) are so named as they were first isolated lysozyme, defensin (cationic protein), phospholipase,
from leucocytes. Firstly, unstable leukotriene A (LTA ) is cathepsin G, elastase, and protease.
4
4
formed which is acted upon by enzymes to form LTB 4 b) Secondary or specific granules contain alkaline phosphatase,
(chemotactic for phagocytic cells and stimulates phagocytic lactoferrin, gelatinase, collagenase, lysozyme, vitamin-B 12
cell adherence) while LTC , LTD and LTE have common binding proteins, plasminogen activator.
4
4
4
actions by causing smooth muscle contraction and thereby c) Tertiary granules or C particles contain gelatinase and acid
induce vasoconstriction, bronchoconstriction and increased hydrolases.
vascular permeability; hence they are also called as slow- Myeloperoxidase causes oxidative lysis by generation of
reacting substances of anaphylaxis (SRS-As). oxygen free radicals, acid hydrolases act within the cell to
General Pathology and Basic Techniques
c) Lipoxins (LX) are a recently described product of cause destruction of bacteria in phagolysosome while prote-
lipooxygenase pathway. Lipooxygenase-12 present in ases attack on the extracellular constituents such as basement
platelets acts on LTA derived from neutrophils and forms membrane, collagen, elastin, cartilage etc.
4
LXA and LXB . Lipoxins act to regulate and counterbalance However, degradation of extracellular components like
4
4
actions of leukotrienes. collagen, basement membrane, fibrin and cartilage by
proteases results in harmful tissue destruction which is kept
3. LYSOSOMAL COMPONENTS. The inflammatory in check by presence of antiproteases like α -antitrypsin and
cells—neutrophils and monocytes, contain lysosomal α -macroglobulin. 1
granules which on release elaborate a variety of mediators 2
of inflammation. These are as under: ii) Granules of monocytes and tissue macrophages. These
cells on degranulation also release mediators of inflammation
like acid proteases, collagenase, elastase and plasminogen
activator. However, they are more active in chronic
inflammation than acting as mediators of acute inflammation.

4. PLATELET ACTIVATING FACTOR (PAF). It is
released from IgE-sensitised basophils or mast cells, other
leucocytes, endothelium and platelets. Apart from its action
on platelet aggregation and release reaction, the actions of
PAF as mediator of inflammation are:
increased vascular permeability;
vasodilatation in low concentration and vasoconstriction
otherwise;
bronchoconstriction;
adhesion of leucocytes to endothelium; and
chemotaxis.
5. CYTOKINES. Cytokines are polypeptide substances pro-
duced by activated lymphocytes (lymphokines) and activated
Figure 6.9 Arachidonic acid metabolites via lipooxygenase pathway. monocytes (monokines). These agents may act on ‘self’ cells